Polymorphs of phenyl pyrrole aminoguandium salts

ABSTRACT

The present disclosure relates to crystalline forms of N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium salts having high solubility. The disclosure also relates to use of said crystalline forms in medicine.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of International Patent ApplicationNo. PCT/EP2022/066884, filed Jun. 21, 2022, which claims priority toEuropean Patent Application No. 21180708.6, filed Jun. 21, 2021, thedisclosures of which are incorporated by reference herein.

TECHNICAL FIELD

The present invention relates to salts ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinehaving a high solubility at low pH.

BACKGROUND

The melanocortin system is a set of neuropeptidergic and immuneendocrinesignalling pathways that play an integral role in the homeostaticcontrol of a diverse array of physiological functions, includingmelanogenesis, stress response, inflammation, immunomodulation andadrenocortical steroidogenesis. It consists of multiple components,including the five G protein-couple melanocortin receptors: melanocortinreceptor 1 (MC1R) to MC5R; peptide ligands; α, β, γ-melanocytestimulating hormone (α, β, γ-MSH); adrenocorticotropic hormone (ACTH)secreted by the anterior pituitary; and endogenous antagonists. Thebiological functions of the melanocortin system are mediated by the fivemelanocortin receptors (MCRs), which have distinct tissue distribution,convey different signalling and exert varying biological activities indifferent organ systems.

Phenyl pyrrole aminoguanidine derivatives with activity on themelanocortin receptors have previously been disclosed. One example ofsuch compound is the anti-inflammatory AP1189(N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine)which was first shown to bind the MC1R and later was identified as abiased dual agonist at receptors MC1R and MC3R that does not provokecanonical cAMP generation (and hence no MC1R-induced melanogenesis) butinstead appear to induce alternative pathways includingERK1/2-phosphorylation and Ca²⁺ mobilisation.

SUMMARY

The present inventors have discovered salts of AP1189 with particularlyfavourable solubility profiles for gastric delivery. The inventors foundthat certain polymorphs of AP1189 salts have very high solubilities,especially at low pH.

Thus, one aspect of the present disclosure provides for a crystallineForm A ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumacetate exhibiting at least X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation at 11.5±0.2,23.5±0.2, and 27.0±0.2.

Another aspect of the present disclosure provides for a crystalline FormB ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsuccinate exhibiting at least X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation at 9.7±0.2,22.8±0.2, and 26.7±0.2.

The present disclosure also provides methods of producing suchcrystalline forms.

One aspect of the present disclosure provides a method for producing theN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumacetate of crystalline Form A as disclosed herein, said methodcomprising:

-   -   i. mixing        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine        and acetic acid in a solvent to form a mixture; and    -   ii. isolating the        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        acetate of crystalline Form A from said mixture.

One aspect of the present disclosure provides a method for producing theN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumacetate of crystalline Form A as disclosed herein, said methodcomprising:

-   -   i. mixing a        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        salt and acetic acid in a solvent to form a mixture; and    -   ii. isolating the        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        acetate of crystalline Form A from the mixture.

One aspect of the present disclosure provides a method for producing theN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumacetate of crystalline Form A as disclosed herein, said methodcomprising:

-   -   i. mixing        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        acetate in a solvent to form a composition; and    -   ii. isolating the        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        acetate of crystalline Form A from said composition.

One aspect of the present disclosure provides a method for producingN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsuccinate of crystalline Form B as disclosed herein, said methodcomprising:

-   -   i. mixing        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine        and succinic acid in a solvent to form a mixture; and    -   ii. isolating the        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        succinate of crystalline Form B from the mixture.

One aspect of the present disclosure provides a method for producingN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsuccinate of crystalline Form B as disclosed herein, said methodcomprising:

-   -   i. mixing a        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        salt and succinic acid in a solvent to form a mixture, and    -   ii. isolating the        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        succinate of crystalline Form B from the mixture.

One aspect of the present disclosure provides a crystalline Form A ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumacetate produced by a method as disclosed herein.

One aspect of the present disclosure provides a crystalline Form B ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsuccinate produced by a method as disclosed herein.

One aspect of the present disclosure provides a pharmaceuticalcomposition comprising the crystalline Form A ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumacetate as disclosed herein and a pharmaceutically acceptable excipient.

One aspect of the present disclosure provides a pharmaceuticalcomposition comprising the crystalline Form B ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsuccinate as disclosed herein and a pharmaceutically acceptableexcipient.

One aspect of the present disclosure provides a method of preparing apharmaceutical composition comprising mixing the crystalline Form A ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumacetate as disclosed herein and a pharmaceutically acceptable excipient.

One aspect of the present disclosure provides a method of preparing apharmaceutical composition, said method comprising mixing thecrystalline Form B ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsuccinate as disclosed herein with a pharmaceutically acceptableexcipient.

One aspect of the present disclosure provides a method of treating adisease or disorder in a subject in need thereof, said method comprisingadministering crystalline Form A ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumacetate as disclosed herein, the crystalline Form B ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsuccinate as disclosed herein, or the pharmaceutical composition asdisclosed herein to a subject in need thereof.

One aspect of the disclosure provides for a use of the crystalline FormA ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumacetate as disclosed herein or the crystalline Form B ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsuccinate as disclosed herein, or the pharmaceutical composition asdisclosed herein, for the manufacture of a medicament for treatment of adisease or disorder.

One aspect of the present disclosure is to provide for crystalline formsof N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalts having high solubility at low pH, e.g. at pH 1.2. Thus, one aspectprovides for a crystalline Form of anN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalt selected from the group consisting of:

-   -   i. a crystalline Form XIV of AP1189 besylate exhibiting at least        X-ray lines (2-theta values) in a powder diffraction pattern        when measured using Cu K_(α) radiation at 13.0±0.2, 15.1±0.2,        and 19.9±0.2,    -   ii. a crystalline Form XIX of AP1189 oxoglutarate exhibiting at        least X-ray lines (2-theta values) in a powder diffraction        pattern when measured using Cu K_(α) radiation at 16.8±0.2,        23.4±0.2, and 23.6±0.2,    -   iii. a crystalline Form XX of AP1189 DL-mandelic acid exhibiting        at least X-ray lines (2-theta values) in a powder diffraction        pattern when measured using Cu K_(α) radiation at 14.8±0.2,        24.2±0.2, and 25.5±0.2,    -   iv. a crystalline Form XXII of AP1189 hippuric exhibiting at        least X-ray lines (2-theta values) in a powder diffraction        pattern when measured using Cu K_(α) radiation at 20.1±0.2,        24.1±0.2, and 24.5±0.2,    -   v. a crystalline Form XXIII of AP1189 formate exhibiting at        least X-ray lines (2-theta values) in a powder diffraction        pattern when measured using Cu K_(α) radiation at 13.3±0.2,        15.1±0.2, and 25.6±0.2,    -   vi. a crystalline Form XXIV of AP1189 DL-lactic acid exhibiting        at least X-ray lines (2-theta values) in a powder diffraction        pattern when measured using Cu K_(α) radiation at 3.8±0.2,        9.9±0.2, and 11.9±0.2,    -   vii. a crystalline Form XXV of AP1189 DL-lactic acid exhibiting        at least X-ray lines (2-theta values) in a powder diffraction        pattern when measured using Cu K_(α) radiation at 9.8±0.2,        11.9±0.2, and 27.6±0.2,    -   viii. a crystalline Form XXVI of AP1189 glutaric acid exhibiting        at least X-ray lines (2-theta values) in a powder diffraction        pattern when measured using Cu K_(α) radiation at 8.3±0.2,        15.9±0.2, and 21.9±0.2, and    -   ix. a crystalline Form XXIX of AP1189 adipic acid exhibiting at        least X-ray lines (2-theta values) in a powder diffraction        pattern when measured using Cu K_(α) radiation at 13.4±0.2,        14.5±0.2, and 25.5±0.2.

One aspect of the present disclosure is to provide crystalline forms ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalts that can be converted into useful crystalline forms ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalts. Thus, one aspect of the present disclosure provides for acrystalline Form of anN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalt selected from the group consisting of:

-   -   i. a crystalline Form III of AP1189 napadisylate exhibiting at        least X-ray lines (2-theta values) in a powder diffraction        pattern when measured using Cu K_(α) radiation at 13.4±0.2,        22.2±0.2, and 26.8±0.2,    -   ii. a crystalline Form IV of AP1189 napadisylate exhibiting at        least X-ray lines (2-theta values) in a powder diffraction        pattern when measured using Cu K_(α) radiation at 5.4±0.2,        15.6±0.2, and 23.4±0.2,    -   iii. a crystalline Form V of AP1189 esylate exhibiting at least        X-ray lines (2-theta values) in a powder diffraction pattern        when measured using Cu K_(α) radiation at 14.5±0.2, 16.5±0.2,        and 18.6±0.2,    -   iv. a crystalline Form VI of AP1189 edisylate exhibiting at        least X-ray lines (2-theta values) in a powder diffraction        pattern when measured using Cu K_(α) radiation at 4.8±0.2,        12.8±0.2, and 16.5±0.2,    -   v. a crystalline Form VII of AP1189 edisylate exhibiting at        least X-ray lines (2-theta values) in a powder diffraction        pattern when measured using Cu K_(α) radiation at 6.1±0.2,        15.7±0.2, and 23.6±0.2,    -   vi. a crystalline Form VIII of AP1189 edisylate exhibiting at        least X-ray lines (2-theta values) in a powder diffraction        pattern when measured using Cu K_(α) radiation at 15.5±0.2,        20.7±0.2, and 21.7±0.2,    -   vii. a crystalline Form IX of AP1189 edisylate exhibiting at        least X-ray lines (2-theta values) in a powder diffraction        pattern when measured using Cu K_(α) radiation at 4.5±0.2,        16.7±0.2, and 24.7±0.2,    -   viii. a crystalline Form X of AP1189 nitrate exhibiting at least        X-ray lines (2-theta values) in a powder diffraction pattern        when measured using Cu K_(α) radiation at 15.3±0.2, 21.4±0.2,        and 25.1±0.2,    -   ix. a crystalline Form XI of AP1189 cyclamate exhibiting at        least X-ray lines (2-theta values) in a powder diffraction        pattern when measured using Cu K_(α) radiation at 7.0±0.2,        13.8±0.2, and 15.7±0.2,    -   x. a crystalline Form XII of AP1189 cyclamate exhibiting at        least X-ray lines (2-theta values) in a powder diffraction        pattern when measured using Cu K_(α) radiation at 7.3±0.2,        15.3±0.2, and 17.9±0.2,    -   xi. a crystalline Form XIII of AP1189 cyclamate exhibiting at        least X-ray lines (2-theta values) in a powder diffraction        pattern when measured using Cu K_(α) radiation at 15.3±0.2,        18.5±0.2, and 18.7±0.2,    -   xii. a crystalline Form XV of AP1189 oxalate exhibiting at least        X-ray lines (2-theta values) in a powder diffraction pattern        when measured using Cu K_(α) radiation at 19.5±0.2, 23.3±0.2,        and 25.8±0.2,    -   xiii. a crystalline Form XVI of AP1189 oxalate exhibiting at        least X-ray lines (2-theta values) in a powder diffraction        pattern when measured using Cu K_(α) radiation at 17.1±0.2,        17.9±0.2, and 19.6±0.2,    -   xiv. a crystalline Form XVII of AP1189 oxalate exhibiting at        least X-ray lines (2-theta values) in a powder diffraction        pattern when measured using Cu K_(α) radiation at 6.3±0.2,        10.6±0.2, and 19.8±0.2,    -   xv. a crystalline Form XVIII of AP1189 (+)-camphor-10-sulfonic        acid exhibiting at least X-ray lines (2-theta values) in a        powder diffraction pattern when measured using Cu K_(α)        radiation at 6.5±0.2, 11.5±0.2, and 14.8±0.2,    -   xvi. a crystalline Form XXI of AP1189 DL-mandelic acid        exhibiting at least X-ray lines (2-theta values) in a powder        diffraction pattern when measured using Cu K_(α) radiation at        5.4±0.2, 10.0±0.2, and 24.6±0.2,    -   xvii. a crystalline Form XXVII of AP1189 glutaric acid further        exhibiting one or more X-ray lines (2-theta values) in a powder        diffraction pattern when measured using Cu K_(α) radiation        selected from the group consisting of 16.9±0.2, 25.6±0.2,        27.1±0.2, 28.2±0.2, and 28.7±0.2, and    -   xviii. a crystalline Form XXVIII of AP1189 glutaric acid        exhibiting at least X-ray lines (2-theta values) in a powder        diffraction pattern when measured using Cu K_(α) radiation at        14.2±0.2, 16.9±0.2, and 24.5±0.2.

One aspect of the present disclosure is to provide forN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalts that can be converted into useful crystalline Forms ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalts. Thus, one aspect of the disclosure provides for a compoundselected from the group consisting of:

-   -   i.        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        succinate,    -   ii.        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        tosylate,    -   iii.        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        fumarate,    -   iv.        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        napadisylate,    -   v.        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        esylate,    -   vi.        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        edisylate,    -   vii.        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        nitrate,    -   viii.        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        cyclamate,    -   ix.        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        besylate,    -   x.        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        oxalate,    -   xi.        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine        (+)-camphor-10-sulfonic acid salt,    -   xii.        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        oxoglutarate,    -   xiii.        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine        DL-mandelic acid salt,    -   xiv.        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine        hippuric acid salt,    -   xv.        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        formate,    -   xvi.        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine        L-lactic acid salt,    -   xvii.        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine        DL-lactic acid salt,    -   xviii.        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine        glutaric acid salt, and    -   xix.        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine        adipic acid salt.

One aspect of the disclosure provides for a composition, apharmaceutical composition, a liquid composition, a unit dosage form, oran oral formulation comprising the crystalline forms ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalt disclosed herein.

One aspect of the disclosure provides for use of such crystalline formof N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalt, composition, pharmaceutical composition, liquid composition, unitdosage form, or oral formulation in medicine.

One aspect of the disclosure provides for use of such crystalline formof N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalt, composition, pharmaceutical composition, liquid composition, unitdosage form, or oral formulation in the treatment of a kidney disease,an arthritic disease, a cardiovascular disease, atherosclerosis, a viraldisease or disorder, or a systemic inflammatory disorder.

DESCRIPTION OF DRAWINGS

FIG. 1 : XRPD diffractogram for AP1189 acetate salt Pattern 1crystallised from acetonitrile.

FIG. 2 : XRPD diffractogram for AP1189 acetate salt Pattern 1 and 2crystallised from ethyl acetate.

FIG. 3 : XRPD diffractogram for AP1189 acetate salt Pattern 3crystallised from THF.

FIG. 4 : XRPD diffractogram for AP1189 tosylate salt Pattern 1crystallised from methanol.

FIG. 5 : XRPD diffractogram for AP1189 fumarate salt Pattern 1crystallised from isopropylalcohol:water 90:10 v/v.

FIG. 6 : XRPD diffractogram for AP1189 succinate salt Pattern 1crystallised from isopropylalcohol:water 90:10 v/v.

FIG. 7 : TGA/DSC thermogram of AP1189 acetate Pattern 1 from1,4-dioxane. Peak temperature: 183.75° C.; onset: 164.62° C.; enthalpy(normalised): 629.95 J/g. Weight loss: 0.001 mg; weight percent loss:0.057%.

FIG. 8 : DSC thermogram of AP1189 acetate Pattern 1 from acetonitrile.Peak temperature 197.86° C.; onset: 192.19° C.; enthalpy (normalised):147.26 J/g.

FIG. 9 : TGA/DSC thermogram of AP1189 acetate Pattern 1 & 2 from2-methyl THF. Peak temperature: 194.18° C.; onset: 171.54° C.; enthalpy(normalised): 475.77 J/g. Weight loss: 0.021 mg; weight percent loss:0.478%.

FIG. 10 : TGA/DSC thermogram of AP1189 acetate Pattern 3 from THF. Peaktemperature: 118.76° C.; onset: 100.62° C.; enthalpy (normalised):138.49 J/g. First weight loss segment: weight loss: 0.002 mg; weightpercent loss: 0.067%. Second weight loss segment: weight loss: 0.672 mg;weight percent loss: 18.610%.

FIG. 11 : TGA/DSC thermogram of AP1189 tosylate Pattern 1 from IPA:water90:10 v/v after storage at 40° C. Peak temperature: 239.24° C.; onset:233.75° C.; enthalpy (normalised): 99.785 J/g. Weight loss: 0.006 mg;weight percent loss: 0.330%.

FIG. 12 : TGA/DSC thermogram of AP1189 fumarate Pattern 1 from2-propanol:water 90:10. Peak temperature: 218.27° C.; onset: 214.61° C.;enthalpy (normalised): 68.467 J/g. WE0.012 mg; weight percent loss:0.319%.

FIG. 13 : DSC thermogram of AP1189 succinate Pattern 1 from IPA:water90:10 v/v. Peak temperature: 196.27° C.; onset: 195.18° C.; enthalpy(normalised): 196.27 J/g.

FIG. 14 : XRPD Diffractogram of AP1189 Napadisylate Pattern 1.

FIG. 15 : XRPD Diffractogram of AP1189 Napadisylate Pattern 2.

FIG. 16 : XRPD Diffractogram of AP1189 Esylate Pattern 1.

FIG. 17 : XRPD Diffractogram of AP1189 Edisylate Pattern 1.

FIG. 18 : XRPD Diffractogram of AP1189 Edisylate Pattern 2.

FIG. 19 : XRPD Diffractogram of AP1189 Edisylate Pattern 4.

FIG. 20 : XRPD Diffractogram of AP1189 Edisylate Pattern 5.

FIG. 21 : XRPD Diffractogram of AP1189 Nitrate Pattern 1.

FIG. 22 : XRPD Diffractogram of AP1189 Cyclamate Pattern 2.

FIG. 23 : XRPD Diffractogram of AP1189 Cyclamate Pattern 4.

FIG. 24 : XRPD Diffractogram of AP1189 Cyclamate Pattern 5.

FIG. 25 : XRPD Diffractogram of AP1189 Besylate Pattern 1.

FIG. 26 : XRPD Diffractogram of AP1189 Oxalate Pattern 1.

FIG. 27 : XRPD Diffractogram of AP1189 Oxalate Pattern 2.

FIG. 28 : XRPD Diffractogram of AP1189 Oxalate Pattern 4.

FIG. 29 : XRPD Diffractogram of AP1189 (+)-Camphor-10-sulfonic acidPattern 1.

FIG. 30 : XRPD Diffractogram of AP1189 Oxoglutarate Pattern 1.

FIG. 31 : XRPD Diffractogram of AP1189 DL-mandelic acid Pattern 2.

FIG. 32 : XRPD Diffractogram of AP1189 DL-mandelic acid Pattern 3.

FIG. 33 : XRPD Diffractogram of AP1189 Hippuric acid Pattern 1.

FIG. 34 : XRPD Diffractogram of AP1189 Formic acid Pattern 1.

FIG. 35 : XRPD Diffractogram of AP1189 DL-Lactic acid Pattern 1.

FIG. 36 : XRPD Diffractogram of AP1189 DL-Lactic acid Pattern 1.

FIG. 37 : XRPD Diffractogram of AP1189 Glutaric acid Pattern 1.

FIG. 38 : XRPD Diffractogram of AP1189 Glutaric acid Pattern 1.

FIG. 39 : XRPD Diffractogram of AP1189 Adipic acid Pattern 1.

FIG. 40 : TG/DSC thermogram of AP1189 Napadisylate Pattern 1. Weightloss: 0.1356 mg. Weight Percent Loss: 3.974%. Enthalpy (normalised):29.422 J/g; Onset x: 87.38° C.; peak temperature: 104.76° C. Enthalpy(normalised): 1.8937 J/g; Peak temperature: 187.47° C.

FIG. 41 : TG/DSC thermogram of AP1189 Esylate Pattern 1. Weight Loss:0.032 mg. Weight Percent Loss: 0.911%. Enthalpy (normalised): 42.119J/g; Onset x: 201.95° C.; Peak temperature: 207.06° C.

FIG. 42 : TG/DSC thermogram of AP1189 Edisylate Pattern 2. Weight Loss:0.061 mg. Weight Percent Loss: 1.175%. Weight Loss: 0.158 mg. WeightPercent Loss: 3.040%. Enthalpy (normalised): 3.1886 J/g; Onset x:220.71° C.; Peak temperature: 224.57° C.

FIG. 43 : TG/DSC thermogram of AP1189 Edisylate Pattern 4. Weight Loss:1.463 mg. Weight Percent Loss: 6.372%. Enthalpy (normalised): 100.17J/g. Onset x: 208.40° C.; Peak temperature: 217.37° C.

FIG. 44 : TG/DSC thermogram of AP1189 Edisylate Pattern 5. Weight Loss:0.120 mg. Weight Percent Loss: 4.701%. Enthalpy (normalised): 54.800J/g; Onset x: 58.52° C.; Peak temperature: 78.51° C. Enthalpy(normalised): 0.93567 J/g; Onset x: Not found; Peak temperature: 151.11°C.

FIG. 45 : TG/DSC thermogram of AP1189 Nitrate Pattern 1. Weight Loss:0.095 mg. Weight Percent Loss: 2.139%. Enthalpy (normalised): 0.4851J/g; Onset x: 178.54° C.; Peak temperature: 182.88° C.

FIG. 46 : TG/DSC thermogram of AP1189 Cyclamate Pattern 2. Weight Loss:0.033 mg. Weight Percent Loss: 0.459%. Enthalpy (normalised): 6.4491J/g; Onset x: 129.90° C.; Peak temperature: 137.27° C.

FIG. 47 : TG/DSC thermogram of AP1189 Cyclamate Pattern 4. Weight Loss:0.041 mg. Weight Percent Loss: 1.080%. Weight Loss: 0.088 mg. WeightPercent Loss: 2.337%. Enthalpy (normalised): 0.0143 J/g; Onset x:133.07° C.; Peak temperature: 138.20° C.

FIG. 48 : TG/DSC thermogram of AP1189 Besylate Pattern 1. Weight Loss:0.014 mg. Weight Percent Loss: 2.369%. Enthalpy (normalised): 48.524J/g; Onset x: 216.45° C.; Peak temperature: 220.49° C.

FIG. 49 : TG/DSC thermogram of AP1189 Oxalate Pattern 1. Weight Loss:0.023 mg. Weight Percent Loss: 1.665%. Enthalpy (normalised): 0.32686J/g; Peak temperature: 210.52° C.

FIG. 50 : TG/DSC thermogram of AP1189 Oxalate Pattern 2. Weight Loss.0.035 mg. Weight Percent Loss: 2.156%. Enthalpy (normalised): 40.935J/g; Onset x: 207.42° C.; Peak temperature: 211.50° C.

FIG. 51 : TG/DSC thermogram of AP1189 Oxalate Pattern 4. Weight Loss:0.016 mg. Weight Percent Loss: 2.164%.

FIG. 52 : TG/DSC thermogram of AP1189 (+)-Camphor-10-sulfonic acidPattern 1. Weight Loss: 0.017 mg. Weight Percent Loss: 1.843%. Enthalpy(normalised): 107.65 J/g; Onset x: 205.38° C.; Peak temperature: 209.93°C.

FIG. 53 : TG/DSC thermogram of AP1189 Oxoglutarate Pattern 1. WeightLoss: 0.167 mg. Weight Percent Loss: 2.379%. Weight Loss: 0.462 mg.Weight Percent Loss: 6.588%. Enthalpy (normalised): 68.335 J/g. Onset x:81.31° C. Peak temperature: 87.92° C.

FIG. 54 : TG/DSC thermogram of AP1189 DL-mandelic acid Pattern 2. WeightLoss: 0.424 mg. Weight Percent Loss: 8.372%. Enthalpy (normalised):43.266 J/g; Onset x: 104.13° C.; Peak temperature: 110.06° C.

FIG. 55 : TG/DSC thermogram of AP1189 DL-mandelic acid Pattern 3. WeightLos: 0.066 mg. Weight Percent Loss: 3.021%. Weight Loss: 0.081 mg.Weight Percent Loss: 3.698%.

FIG. 56 : TG/DSC thermogram of AP1189 Hippuric acid Pattern 1. WeightLoss: 0.022 mg. Weight Percent Loss: 1.294%. Weight Loss: 0.026 mg.Weight Percent Loss: 1.495%. Enthalpy (normalised): 4.7263 J/g; Onset x:138.92° C.; Peak temperature: 149.72° C.

FIG. 57 : FT-IR Spectrum of AP1189 Napadisylate Pattern 1.

FIG. 58 : FT-IR Spectrum of AP1189 Napadisylate Pattern 2.

FIG. 59 : FT-IR Spectrum of AP1189 Esylate Pattern 1.

FIG. 60 : FT-IR Spectrum of AP1189 Edisylate Pattern 2.

FIG. 61 : FT-IR Spectrum of AP1189 Edisylate Pattern 4.

FIG. 62 : FT-IR Spectrum of AP1189 Edisylate Pattern 5.

FIG. 63 : FT-IR Spectrum of AP1189 Nitrate Pattern 1.

FIG. 64 : FT-IR Spectrum of AP1189 Cyclamate Pattern 2.

FIG. 65 : FT-IR Spectrum of AP1189 Cyclamate Pattern 4.

FIG. 66 : FT-IR Spectrum of AP1189 Cyclamate Pattern 5.

FIG. 67 : FT-IR Spectrum of AP1189 Besylate Pattern 1.

FIG. 68 : FT-IR Spectrum of AP1189 Oxalate Pattern 1.

FIG. 69 : FT-IR Spectrum of AP1189 Oxalate Pattern 2.

FIG. 70 : FT-IR Spectrum of AP1189 Oxalate Pattern 4.

FIG. 71 : FT-IR Spectrum of AP1189 (+)-Camphor-10-sulfonic acid Pattern1.

FIG. 72 : FT-IR Spectrum of AP1189 Oxoglutarate Pattern 1.

FIG. 73 : FT-IR Spectrum of AP1189 DL-mandelic acid Pattern 2.

FIG. 74 : FT-IR Spectrum of AP1189 DL-mandelic acid Pattern 3.

FIG. 75 : FT-IR Spectrum of AP1189 Hippuric acid Pattern 1.

FIG. 76 : FT-IR Spectrum of AP1189 Formic acid Pattern 1.

FIG. 77 : FT-IR Spectrum of AP1189 DL-Lactic acid Pattern 1.

FIG. 78 : FT-IR Spectrum of AP1189 DL-Lactic acid Pattern 1.

FIG. 79 : FT-IR Spectrum of AP1189 Glutaric acid Pattern 1.

FIG. 80 : FT-IR Spectrum of AP1189 Glutaric acid Pattern 2.

FIG. 81 : TG/DSC thermogram of AP1189 Napadisylate Pattern 2. WeightLoss: 0.157 mg. Weight Percent Loss: 7.940%.

FIG. 82 : TG/DSC thermogram of AP1189 Edisylate Pattern 1. Weight Loss:0.082 mg. Weight Percent Loss: 4.634%. Enthalpy (normalised): 3.2707J/g; Onset x: 69.98° C.; Peak temperature: 78.37° C. Enthalpy(normalised): 0.83635 J/g; Peak temperature: 151.31° C.

FIG. 83 : TG/DSC thermogram of AP1189 Cyclamate Pattern 5. Weight Loss:0.070 mg. Weight Percent Loss: 1.696%. Enthalpy (normalised): 0.68855J/g; Onset x: 140.91° C.; Peak temperature: 146.39° C.

FIG. 84 : TG/DSC thermogram of AP1189 Formic acid Pattern 1. WeightLoss: 0.008 mg. Weight Percent Loss: 3.049%. Enthalpy (normalised):7.5282 J/g; Onset x: 169.12° C.; Peak temperature: 171.97° C.

FIG. 85 : TG/DSC thermogram of AP1189 DL-Lactic acid Pattern 1. WeightLoss: 0.026 mg. Weight Percent Loss: 0.859%. Enthalpy (normalised):31.499 J/g. Onset x: 189.47° C. Peak temperature: 192.80° C.

FIG. 86 : TG/DSC thermogram of AP1189 DL-Lactic acid Pattern 1. WeightLoss: 0.034 mg. Weight Percent Loss: 1.476%. Enthalpy (normalised):2.2523 J/g; Onset x: 198.48° C.; Peak temperature: 200.63° C.

FIG. 87 : TG/DSC thermogram of AP1189 Glutaric acid Pattern 1. WeightLoss: 0.27 mg. Weight Percent Loss: 1.256%. Enthalpy (normalised):0.0964 J/g; Onset x: 109.24° C.; Peak temperature: 115.31° C. Enthalpy(normalised): 16.647 J/g; Onset x: 159.93° C.; Peak temperature: 164.02°C.

FIG. 88 : TG/DSC thermogram of AP1189 Glutaric acid Pattern 2. WeightLoss: 0.019 mg. Weight Percent Loss: 1.001%. Enthalpy (normalised):48.550 J/g; Onset x: 162.77° C.; Peak temperature: 165.94° C.

FIG. 89 : TG/DSC thermogram of AP1189 Glutaric acid Pattern 4. WeightLoss: 0.010 mg. Weight Percent Loss: 1.764%. Enthalpy (normalised):18.475 J/g; Onset x: 114.55° C.; Peak temperature: 148.15° C. Enthalpy(normalised): 10.102 J/g; Onset x: 160.45° C.; Peak temperature: 163.28°C.

FIG. 90 : TG/DSC thermogram of AP1189 Adipic acid Pattern 1. WeightLoss: 0.015 mg. Weight Percent Loss: 6.117%. Enthalpy (normalised):12.428 J/g. Onset x: 183.34° C.; Peak temperature: 187.98° C.

FIG. 91 : XRPD Diffractogram of AP1189 Glutaric acid Pattern 4.

FIG. 92 : IR spectrum of AP1189 acetate Pattern 1.

DETAILED DESCRIPTION Definitions

By a “compound of formula I”, “compound I”, and “AP1189” is meant thecompoundN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine,which has the chemical structure of formula I:

as well as tautomers and stereoisomers thereof. Another name for thecompound isN″-[(E)-[(2E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]prop-2-en-1-ylidene]amino]guanidine.

In some instances the term “AP1189” may refer to either the free basestructure of Formula I or it may refer to the acetate salt of AP1189.Preferable, the term “AP1189 free base” refers to the structure ofFormula I. Preferably, the term “AP1189 acetate” refers to the acetatesalt of the structure of Formula I.

As used herein, the term “SP1189” refers to the succinate salt of thestructure of Formula I. The terms “SP1189” and “AP1189 succinate” aresynonymous as used herein.

Regarding the naming of salts, it is to be construed that terms such as“N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidineacetate” andN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumacetate” are synonymous, i.e. when an anion is written immediately after“N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine”,then the protonated form of“N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine” ismeant, i.e.“N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium”.Similarly, when an acid is written as part of the name of a protonatedcompound, e.g.“N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumacetic acid”, then the non-protonated form is meant of that compound,e.g. “N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidineacetic acid” is meant. These considerations also apply to other salts ofthe disclosed compound.

In one embodiment, the compound of the disclosureN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine,including tautomers and stereoisomers thereof. In one embodiment, thecompound of the disclosure isN-{(1E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine,including tautomers and stereoisomers thereof. In one embodiment, thecompound of the disclosure isN″-[(E)-[3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]prop-2-en-1-ylidene]amino]guanidine,including tautomers and stereoisomers thereof.

In one embodiment, the compound of the disclosure isN-{(2E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine,including tautomers and stereoisomers thereof. In one embodiment, thecompound of the disclosure isN″-[[(2E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]prop-2-en-1-ylidene]amino]guanidine,including tautomers and stereoisomers thereof.

In one embodiment, the compound of the disclosure isN-{(1E,2E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine(also termed(E)-N-trans-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidineherein)), including tautomers thereof. In one embodiment, the compoundof the disclosure isN″-[(E)-[(2E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]prop-2-en-1-ylidene]amino]guanidine,including tautomers thereof. These compounds may also appear as thesalts and corresponding crystalline forms disclosed herein. In oneembodiment, the compound of the disclosure is selected from the groupconsisting ofN-{(1Z)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine,N-{(2Z)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine,N-{(1Z,2Z)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine,N-{(1Z,2E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine,andN-{(1E,2Z)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine.

In one embodiment, the compound of the disclosure is selected from thegroup consisting ofN″-[(Z)-[3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]prop-2-en-1-ylidene]amino]guanidine,N″-[[(2Z)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]prop-2-en-1-ylidene]amino]guanidine,N″-[(Z)-[(2Z)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]prop-2-en-1-ylidene]amino]guanidine,N″-[(Z)-[(2E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]prop-2-en-1-ylidene]amino]guanidine,andN″-[(E)-[(2Z)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]prop-2-en-1-ylidene]amino]guanidine.

In a preferred embodiment, the alkene moiety of the compound is in the Econfiguration, and the imine moiety is in the Z or the E configuration.In one embodiment, the compound is a mixture ofN″-[(E)-[(2E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]prop-2-en-1-ylidene]amino]guanidineandN″-[(Z)-[(2E)-3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]prop-2-en-1-ylidene]amino]guanidine.

The compound of the disclosure may additionally be any tautomer of theabove structures. As used herein, “tautomer” means other structuralisomers that exist in equilibrium resulting from the migration of ahydrogen atom. In reporting results of a measurement, such as themeasurement of a 2-theta value, e.g. the reading of a 2-theta value froman XRPD diffractogram, the skilled person will understand that themethod of measuring the value inherently comprises some degree ofuncertainty. For example, measurements of 2-theta values may have anuncertainty of 0.2°.

By a crystalline “Form A” of AP1189 acetate is meant the crystallineform of AP1189 acetate that exhibits the X-ray lines (2-theta values) ina powder diffraction pattern when measured using Cu K_(α) radiationcorresponding to AP1189 acetate Pattern 1 as disclosed herein.

By a crystalline “Form B” of AP1189 succinate is meant the crystallineform of AP1189 succinate that exhibits the X-ray lines (2-theta values)in a powder diffraction pattern when measured using Cu K_(α) radiationcorresponding to AP1189 succinate Pattern 1 as disclosed herein.

Unless otherwise specified, the unit of 2-theta values is degrees (°).

By “onset temperature” is meant the designed intersection point of theextrapolated baseline and the inflectional tangent at the beginning ofthe melting.

As used herein, “seeding” refers to the technique of adding a “seed”crystal to the crystallization solution to promote the formation ofcrystals. Preferably, the composition of the seed crystal is the same asthe composition of the crystals being formed.

Compounds

In one embodiment, the present disclosure provides the compound AP1189,specifically a salt thereof. One embodiment provides for the compoundAP1189, including tautomeric forms thereof and/or isomeric formsthereof, such as enantiomeric forms and/or diastereomeric forms thereof.In one embodiment, the diastereomeric forms comprise cis and trans formsof the compound, specifically with respect to the alkene moiety. Thecompound may also exist as either the E or Z form with respect to theC═N double bond of the structure of Formula I. The person of skill inthe art understands that in certain instances, E configuration issynonymous to trans configuration, and that in certain instances, Zconfiguration is synonymous to cis configuration. For example, in thespecific case where both of the atoms forming part of a double bond areeach bound to exactly 1 further moiety that is not a hydrogen moiety ora lone pair. One embodiment of the present disclosure provides for theacetate salt of AP1189. Another embodiment of the present disclosureprovides for the succinate salt of AP1189. In one embodiment the term“compound of the disclosure” means the crystalline Form A of AP1189acetate. In one embodiment the term “compound of the disclosure” meansthe crystalline Form B of AP1189 succinate.

In some embodiments, the pharmaceutically acceptable salt of AP1189 isselected from the group consisting of:

-   (E)-N-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl-allylideneamino]-guanidinium    acetate, including tautomeric and stereoisomeric forms thereof;-   (E)-N-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl-allylideneamino]-guanidinium    succinate, including tautomeric and stereoisomeric forms thereof;-   (E)-N-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl-allylideneamino]-guanidine    DL-mandelic acid salt, including tautomeric and stereoisomeric forms    thereof;-   (E)-N-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl-allylideneamino]-guanidine    hippuric acid salt, including tautomeric and stereoisomeric forms    thereof;-   (E)-N-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl-allylideneamino]-guanidine    L-lactic acid salt, including tautomeric and stereoisomeric forms    thereof; >50 mM-   (E)-N-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl-allylideneamino]-guanidinium    besylate, including tautomeric and stereoisomeric forms thereof;-   (E)-N-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl-allylideneamino]-guanidinium    oxoglutarate, including tautomeric and stereoisomeric forms thereof;-   (E)-N-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl-allylideneamino]-guanidine    formic acid salt, including tautomeric and stereoisomeric forms    thereof;-   (E)-N-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl-allylideneamino]-guanidine    DL-lactic acid salt, including tautomeric and stereoisomeric forms    thereof;-   (E)-N-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl-allylideneamino]-guanidine    glutaric acid salt, including tautomeric and stereoisomeric forms    thereof;-   (E)-N-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl-allylideneamino]-guanidine    adipic acid salt, including tautomeric and stereoisomeric forms    thereof; and-   (E)-N-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl-allylideneamino]-guanidinium    nitrate salt, including tautomeric and stereoisomeric forms thereof.

In one embodiment, a pharmaceutically acceptable salt of AP1189 isselected from the group consisting of the acetate salt of AP1189, thesuccinate salt of AP1189, the DL-mandelic acid salt of AP1189, thehippuric acid salt of AP1189, the L-lactic acid salt of AP1189, thebesylate salt of AP1189, the oxoglutarate salt of AP1189, the formicacid salt of AP1189, the DL-lactic acid salt of AP1189, the glutaricacid salt of AP1189, the adipic acid salt of AP1189 and the nitrate saltof AP1189.

One embodiment provides for a salt of AP1189 selected from the groupconsisting of:

-   (E)-N-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl-allylideneamino]-guanidinium    napadisylate, including tautomeric and stereoisomeric forms thereof;-   (E)-N-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl-allylideneamino]-guanidinium    esylate, including tautomeric and stereoisomeric forms thereof;-   (E)-N-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl-allylideneamino]-guanidinium    edisylate, including tautomeric and stereoisomeric forms thereof;-   (E)-N-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl-allylideneamino]-guanidinium    cyclamate, including tautomeric and stereoisomeric forms thereof;-   (E)-N-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl-allylideneamino]-guanidinium    oxalate, including tautomeric and stereoisomeric forms thereof; and-   (E)-N-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl-allylideneamino]-guanidine    (+)-Camphor-10-sulfonic acid salt, including tautomeric and    stereoisomeric forms thereof.

The terms “treatment” and “treating” as used herein refer to themanagement and care of a subject for the purpose of combating acondition, disease or disorder. The term is intended to include the fullspectrum of treatments for a given condition from which the subject issuffering. The subject to be treated is preferably a mammal, inparticular a human being. Treatment of animals, such as mice, rats,dogs, cats, horses, cows, sheep and pigs, is, however, also within thescope of the present context. The subjects to be treated can be ofvarious ages.

It is an aspect of the present disclosure to provide an oral formulationas disclosed herein comprising a crystalline form of an AP1189 saltdisclosed herein, for use in the treatment of a disease or disorder in asubject, wherein the subject to be treated is a mammal. In someembodiment the mammal is a human being. In some embodiments the mammalis a domestic animal. In some embodiments the mammal is selected fromthe group consisting of mice, rats, dogs, cats, horses, cows, sheep andpigs.

Crystalline Forms

The present disclosure relates to crystalline forms ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalts. It is an object of the disclosure to provide crystalline forms ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalts having high solubility in aqueous medium, particularly at low pH.It is likewise an object of the disclosure to provide crystalline formsof N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalts having high dissolution rate in aqueous medium, particularly atlow pH.

Crystalline forms of AP1189 and salts thereof may be characterised byX-Ray Powder Diffraction (XRPD) analysis. Such analysis may be carriedout using a suitable X-ray powder diffractometer such as a PANalyticalX'pert pro with PIXcel detector (128 channels). Scanning of samples maybe performed between 3 and 35° 2θ. Samples may be gently ground prior tomeasurement to release any agglomerates. Samples may be loaded onto amulti-well plate with Kapton or Mylar polymer film to support thesample. Measurements may be carried out by placing the multi-well platein the diffractometer followed by analysis using Cu K radiation (α1λ=1.54060 Å; α2=1.54443 Å; β=1.39225 Å; α1:α2 ratio=0.5) running intransmission mode (step size 0.0130° 2θ, step time 18.87 s) using 40kV/40 mA generator settings.

Table 1 shows an overview of the polymorphs disclosed herein

TABLE 1 overview of polymorphs Salt and polymorph XRPD FiguresCounterion trivial form of AP1189 pattern XRPD TGA/DSC FT-IR and/orsystematic name Acetate Form A 1 1 7, 8 Acetic acid Acetate Form I 1 + 22 9 Acetic acid Succinate Form B 1 6 13 Succinic acid Tosylate Form C 14 11 Toluenesulfonic acid Fumarate Form D 1 5 12 (2E)-But-2-enedioicacid Acetate Form II 3 3 10 Acetic acid Napadisylate Form III 1 14 40 57Naphthalene-1,5-disulfonic acid Napadisylate Form IV 2 15 81 58Naphthalene-1,5-disulfonic acid Esylate Form V 1 16 41 59 Ethanesulfonicacid Edisylate Form VI 1 17 82 Ethane-1,2-disulfonic acid Edisylate FormVII 2 18 42 60 Ethane-1,2-disulfonic acid Edisylate Form VIII 4 19 43 61Ethane-1,2-disulfonic acid Edisylate Form IX 5 20 44 62Ethane-1,2-disulfonic acid Nitrate Form X 1 21 45 63 Nitric acidCyclamate Form XI 2 22 46 64 Cyclohexylsulfamic acid Cyclamate Form XII4 23 47 65 Cyclohexylsulfamic acid Cyclamate Form XIII 5 24 83 66Cyclohexylsulfamic acid Besylate Form XIV 1 25 48 67 Benzenesulfonicacid Oxalate Form XV 1 26 49 68 Oxalic acid Oxalate Form XVI 2 27 50 69Oxalic acid Oxalate Form XVII 4 28 51 70 Oxalic acid(+)-Camphor-10-sulfonic 1 29 52 71 (+)-Camphor-10-sulfonic acid acidForm XVIII Oxoglutarate Form XIX 1 30 53 72 2-oxoglutaric acid,ketoglutaric acid, 2-oxopentanedioic acid α-ketoglutaric acidalpha-ketoglutaric acid DL-Mandelic acid Form XX 2 31 54 73Hydroxy(phenyl)acetic acid DL-Mandelic acid Form XXI 3 32 55 74Hydroxy(phenyl)acetic acid Hippuric acid Form XXII 1 33 56 75N-Benzoylglycine Formic acid Form XXIII 1 34 84 76 Formic acid L-Lacticacid Form XXIV 1 35 85 77 2-Hydroxypropanoic acid DL-Lactic acid FormXXV 1 36 86 78 2-Hydroxypropanoic acid Glutaric acid Form XXVI 1 37 8779 Pentanedioic acid Glutaric acid Form XXVII 2 38 88 80 Pentanedioicacid Glutaric acid Form XXVIII 4 91 89 Pentanedioic acid Adipic acidForm XXIX 1 39 90 Hexanedioic acid

AP1189 Acetate Form A

The present disclosure provides for a crystalline Form A of AP1189acetate. Crystalline Form A of AP1189 acetate exhibits an XRPDdiffractogram as shown in FIG. 1 . One embodiment of the presentdisclosure provides for a crystalline Form A of AP1189 acetateexhibiting at least X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation at 11.5±0.2, 23.5±0.2,and 27.0±0.2. One embodiment provides for a crystalline Form A of AP1189acetate further exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 11.7±0.2, 13.0±0.2, 15.5±0.2,15.6±0.2, 16.2±0.2, 19.6±0.2, 20.0±0.2, 21.1±0.2, and 24.8±0.2. Oneembodiment of the present disclosure provides for a crystalline Form Aof AP1189 acetate exhibiting an X-ray pattern (2-theta values) in apowder diffraction when measured using Cu K_(α) radiation according toFIG. 1 .

One embodiment of the disclosure provides for a crystalline Form A ofAP1189 acetate exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 6.1, 11.5, 11.7, 12.2, 13.0, 15.5,15.6, 15.9, 16.2, 18.3, 18.6, 19.6, 20.0, 20.6, 21.1, 21.5, 21.8, 22.3,23.5, 24.8, 25.7, 27.0, 27.5, 28.2, 28.5, 30.2, 30.7, 31.2, 32.3, 32.9,33.4, and 34.3.

One embodiment of the disclosure provides for a crystalline Form A ofAP1189 acetate exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 6.1±0.2, 11.5±0.2, 11.7±0.2,12.2±0.2, 13.0±0.2, 15.5±0.2, 15.6±0.2, 15.9±0.2, 16.2±0.2, 18.3±0.2,18.6±0.2, 19.6±0.2, 20.0±0.2, 20.6±0.2, 21.1±0.2, 21.5±0.2, 21.8±0.2,22.3±0.2, 23.5±0.2, 24.8±0.2, 25.7±0.2, 27.0±0.2, 27.5±0.2, 28.2±0.2,28.5±0.2, 30.2±0.2, 30.7±0.2, 31.2±0.2, 32.3±0.2, 32.9±0.2, 33.4±0.2,and 34.3±0.2. It may be advantageous to identify the crystalline Form Aof AP1189 acetate by X-ray lines (2-theta values) having a high relativeintensity, and/or by characteristic X-ray lines. Thus, one embodiment ofthe present disclosure provides for a crystalline Form A of AP1189acetate exhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 11.5, 11.7, 13.0, 15.5, 15.6, 16.2, 19.6, 20.0,21.1, 23.5, 24.8, and 27.0. One embodiment of the present disclosureprovides for a crystalline Form A of AP1189 acetate exhibiting one ormore X-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of11.5±0.2, 11.7±0.2, 13.0±0.2, 15.5±0.2, 15.6±0.2, 16.2±0.2, 19.6±0.2,20.0±0.2, 21.1±0.2, 23.5±0.2, 24.8±0.2, and 27.0±0.2. One embodiment ofthe present disclosure provides for a crystalline Form A of AP1189acetate exhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of the 2-theta values in listed in Table 2.

AP1189 Acetate Form I

Another crystalline form of AP1189 acetate has been identified hereinwhich exhibits a mixture of a XRPD Pattern 1 and XRPD Pattern 2. In apreferred embodiment, the crystalline Form A of AP1189 acetate issubstantially free of the polymorph of AP1189 acetate, which gives riseto XRPD Pattern 2. In one embodiment, “substantially free” means thatthe crystalline Form A of AP1189 acetate comprises less than 90% of thepolymorph of AP1189 acetate which gives rise to XRPD Pattern 2, such asless than 80%, such as less than 70%, such as less than 60%, such asless than 50%, such as less than 40%, such as less than 30%, such asless than 20%, such as less than 15%, such as less than 10%, such asless than 5% of the polymorph of AP1189 acetate, which gives rise toXRPD Pattern 2. The content of the polymorph of AP1189 acetate, whichgives rise to XRPD Pattern 2, may be assessed by the intensity of X-raylines of Pattern 2 relative to the intensity of the X-ray lines ofPattern 1 of AP1189 acetate. For example, Pattern 2 exhibits X-ray linesat (2-theta values) 14.9, 18.0, and 24.2 which do not overlap with X-raylines originating from Pattern 1 of AP1189. Thus, one embodiment of thepresent disclosure provides for a crystalline Form A of AP1189 acetatesubstantially free of a second crystalline form of AP1189 acetate, thesecond crystalline form of AP1189 acetate exhibits X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation at 14.9±0.2, 18.0±0.2, and/or 24.2±0.2. One embodiment of thepresent disclosure provides for a crystalline Form A of AP1189 acetatesubstantially free of a second crystalline form of AP1189 acetate, thesecond crystalline form of AP1189 acetate exhibits X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation at 14.9, 18.0, and/or 24.2. In one embodiment of the presentdisclosure, the crystalline Form A of AP1189 acetate exhibits no X-raylines at 14.9±0.2, 18.0 0.2, and/or 24.2±0.2 in an powder diffractionpattern, or the crystalline Form A of AP1189 acetate exhibits lines at14.9±0.2, 18.0±0.2, and/or 24.2±0.2 that have a relative intensity lessthan 30%, such as less than 25%, such as less than 20%, such as lessthan 15%, such as less than 10%, such as less than 5%.

AP1189 Succinate Form B

The present disclosure provides for a crystalline Form B of AP1189succinate. Crystalline Form B of AP1189 succinate exhibits an XRPDdiffractogram as shown in FIG. 6 . One embodiment of the presentdisclosure provides for a crystalline Form B of AP1189 succinateexhibiting at least X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation at 9.7±0.2, 22.8±0.2, and26.7±0.2. One embodiment provides for a crystalline Form B of AP1189succinate further exhibiting one or more X-ray lines (2-theta values) ina powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 5.4±0.2, 13.4±0.2, 16.3±0.2, and19.5±0.2. One embodiment of the present disclosure provides for acrystalline Form B of AP1189 succinate further exhibiting one or moreX-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of12.2±0.2, 15.8±0.2, 21.8±0.2, and 28.5±0.2. One embodiment of thedisclosure provides for a crystalline Form B of AP1189 succinateexhibiting an X-ray pattern (2-theta values) in a powder diffractionwhen measured using Cu K_(α) radiation according to FIG. 6 .

One embodiment of the disclosure provides for a crystalline Form B ofAP1189 succinate exhibiting one or more X-ray lines (2-theta values) ina powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 5.4, 9.7, 12.2, 12.7, 13.4, 13.6,15.8, 16.3, 18.1, 18.6, 18.9, 19.5, 19.9, 21.1, 21.8, 21.8, 22.0, 22.2,22.4, 22.8, 23.4, 23.7, 24.6, 25.0, 25.3, 26.1, 26.3, 26.7, 27.5, 28.5,29.1, 29.4, 30.0, 31.5, 32.3, 32.7, 33.6, and 34.1. One embodiment ofthe disclosure provides for a crystalline Form B of AP1189 succinateexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 5.4±0.2, 9.7±0.2, 12.2±0.2, 12.7±0.2, 13.4±0.2,13.6±0.2, 15.8±0.2, 16.3±0.2, 18.1±0.2, 18.6±0.2, 18.9±0.2, 19.5±0.2,19.9±0.2, 21.1±0.2, 21.8±0.2, 21.8±0.2, 22.0±0.2, 22.2±0.2, 22.4±0.2,22.8±0.2, 23.4±0.2, 23.7±0.2, 24.6±0.2, 25.0±0.2, 25.3±0.2, 26.1±0.2,26.3±0.2, 26.7±0.2, 27.5±0.2, 28.5±0.2, 29.1±0.2, 29.4±0.2, 30.0±0.2,31.5±0.2, 32.3±0.2, 32.7±0.2, 33.6±0.2, and 34.1±0.2. It may beadvantageous to identify the crystalline Form B of AP1189 succinate byX-ray lines (2-theta values) having a high relative intensity, and/or bycharacteristic X-ray lines. Thus, one embodiment of the presentdisclosure provides for a crystalline Form B of AP1189 succinateexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 5.4, 9.7, 12.2, 13.4, 15.8, 16.3, 19.5, 21.8,22.8, 26.7, and 28.5. One embodiment of the present disclosure providesfor a crystalline Form B of AP1189 succinate exhibiting one or moreX-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of5.4±0.2, 9.7±0.2, 12.2±0.2, 13.4±0.2, 15.8±0.2, 16.3±0.2, 19.5±0.2,21.8±0.2, 22.8±0.2, 26.7±0.2, and 28.5±0.2. One embodiment of thepresent disclosure provides for a crystalline Form B of AP1189 succinateexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of the 2-theta values in listed in Table 7.

AP1189 Acetate Form II

One embodiment provides for crystalline forms ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumacetate, which may be converted to AP1189 acetate of crystalline Form A.One embodiment provides for a crystalline Form I of AP1189 acetatecorresponding to XRPD Pattern 1 and 2. A specific embodiment providesfor a crystalline Form I of AP1189 acetate exhibiting X-ray lines(2-theta values) in a powder diffraction pattern when measured using CuK_(α) radiation at one or more of 11.5±0.2, 11.7±0.2, 12.9±0.2,14.9±0.2, 15.4±0.2, 15.6±0.2, 18.0±0.2, 19.9±0.2, 20.0±0.2, 21.1±0.2,21.5±0.2, 21.8±0.2, 22.4±0.2, 23.5±0.2, 24.2±0.2, 24.7±0.2, and26.9±0.2.

One embodiment provides for a crystalline Form I of AP1189 acetateexhibiting X-ray lines (2-theta values) in a powder diffraction patternwhen measured using Cu K_(α) radiation as shown in FIG. 2 . Oneembodiment of the present disclosure provides for a crystalline Form IIof AP1189 acetate corresponding to XRPD Pattern 3. A specific embodimentprovides for a crystalline Form II of AP1189 acetate exhibiting X-raylines (2-theta values) in a powder diffraction pattern when measuredusing Cu K_(α) radiation at one or more of 7.5±0.2, 9.4±0.2, 12.8±0.2,13.3±0.2, 14.2±0.2, 15.3±0.2, 16.0±0.2, 17.0±0.2, 18.8±0.2, 19.7±0.2,20.3±0.2, 21.1±0.2, 21.4±0.2, 21.9±0.2, 22.0±0.2, 22.7±0.2, and23.1±0.2. One embodiment provides for a crystalline Form II of AP1189acetate exhibiting X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation as shown in FIG. 3 .

AP1189 Solid and/or Amorphous Forms

One embodiment of the present disclosure provides for a solid form ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsuccinate. One embodiment of the present disclosure provides for asolid, amorphous form ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsuccinate.

AP1189 Tosylate Form C

The disclosure also provides for a crystalline Form C of AP1189tosylate. Crystalline Form C of AP1189 tosylate exhibits an XRPDdiffractogram as shown in FIG. 4 . One embodiment of the presentdisclosure provides for a crystalline Form C of AP1189 tosylateexhibiting at least X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation at 14.5±0.2, 21.0±0.2,and 25.2±0.2. In one embodiment of the present disclosure, thecrystalline Form C of AP1189 tosylate further exhibits one or more X-raylines (2-theta values) in a powder diffraction pattern when measuredusing Cu K_(α) radiation selected from the group consisting of 13.4±0.2and 16.0±0.2. In one embodiment of the present disclosure, thecrystalline Form C of AP1189 tosylate further exhibits one or more X-raylines (2-theta values) in a powder diffraction pattern when measuredusing Cu K_(α) radiation selected from the group consisting of 8.0±0.2,9.4±0.2, 10.0±0.2, 15.3±0.2, 16.7±0.2, 17.6±0.2, 19.2±0.2, 19.8±0.2,21.3±0.2, and 25.4±0.2. In one embodiment, the crystalline Form C ofAP1189 tosylate exhibits an X-ray pattern (2-theta values) in a powderdiffraction when measured using Cu K_(α) radiation according to FIG. 4 .

One embodiment of the disclosure provides for a crystalline Form C ofAP1189 tosylate exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 8.0, 9.4, 10.0, 10.8, 12.1, 12.3,13.4, 14.1, 14.5, 15.3, 15.7, 16.0, 16.7, 17.6, 19.2, 19.8, 20.0, 20.7,21.0, 21.3, 22.0, 22.4, 22.7, 22.8, 23.1, 23.6, 24.1, 24.3, 25.2, 25.4,25.7, 26.1, 26.7, 27.1, 27.7, 28.1, 29.0, 29.2, 29.9, 30.3, 30.7, 31.4,32.7, 33.2, 33.5, and 34.1. 34.6. One embodiment of the disclosureprovides for a crystalline Form C of AP1189 tosylate exhibiting one ormore X-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of8.0±0.2, 9.4±0.2, 10.0±0.2, 10.8±0.2, 12.1±0.2, 12.3±0.2, 13.4±0.2,14.1±0.2, 14.5±0.2, 15.3±0.2, 15.7±0.2, 16.0±0.2, 16.7±0.2, 17.6±0.2,19.2±0.2, 19.8±0.2, 20.0±0.2, 20.7±0.2, 21.0±0.2, 21.3±0.2, 22.0±0.2,22.4±0.2, 22.7±0.2, 22.8±0.2, 23.1±0.2, 23.6±0.2, 24.1±0.2, 24.3±0.2,25.2±0.2, 25.4±0.2, 25.7±0.2, 26.1±0.2, 26.7±0.2, 27.1±0.2, 27.7±0.2,28.1±0.2, 29.0±0.2, 29.2±0.2, 29.9±0.2, 30.3±0.2, 30.7±0.2, 31.4±0.2,32.7±0.2, 33.2±0.2, 33.5±0.2, and 34.1±0.2. It may be advantageous toidentify the crystalline Form C of AP1189 tosylate by X-ray lines(2-theta values) having a high relative intensity, and/or bycharacteristic X-ray lines. Thus, one embodiment of the presentdisclosure provides for a crystalline Form C of AP1189 tosylateexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 8.0, 9.4, 10.0, 13.4, 14.5, 15.3, 16.0, 16.7,17.6, 19.2, 19.8, 21.0, 21.3, 25.2, and 25.4. One embodiment of thepresent disclosure provides for a crystalline Form C of AP1189 tosylateexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 8.0±0.2, 9.4±0.2, 10.0 0.2, 13.4±0.2, 14.5±0.2,15.3±0.2, 16.0±0.2, 16.7±0.2, 17.6±0.2, 19.2±0.2, 19.8±0.2, 21.0±0.2,21.3±0.2, 25.2±0.2, and 25.4±0.2. One embodiment of the presentdisclosure provides for a crystalline Form C of AP1189 tosylateexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of the 2-theta values in listed in Table 5.

AP1189 Fumarate Form D

The disclosure also provides for a crystalline Form D of AP1189fumarate. Crystalline Form D of AP1189 fumarate exhibits an XRPDdiffractogram as shown in FIG. 5 . One embodiment of the presentdisclosure provides for a crystalline Form D of AP1189 fumarateexhibiting at least X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation at 17.6±0.2, 21.2±0.2,and 26.3±0.2. In one embodiment of the present disclosure, thecrystalline Form D of AP1189 fumarate further exhibits one or more X-raylines (2-theta values) in a powder diffraction pattern when measuredusing Cu K_(α) radiation selected from the group consisting of 11.5±0.2,21.9±0.2, and 23.9±0.2. In one embodiment of the present disclosure, thecrystalline Form D of AP1189 fumarate further exhibits one or more X-raylines (2-theta values) in a powder diffraction pattern when measuredusing Cu K_(α) radiation selected from the group consisting of 9.2±0.2,10.5±0.2, 10.9±0.2, 11.9±0.2, 15.8±0.2, 18.7±0.2, 19.4±0.2, 23.4±0.2,and 24.5±0.2. In one embodiment, the crystalline Form D of AP1189fumarate exhibits an X-ray pattern (2-theta values) in a powderdiffraction when measured using Cu K_(α) radiation according to FIG. 5 .

One embodiment of the disclosure provides for a crystalline Form D ofAP1189 fumarate exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 8.6, 9.2, 10.2, 10.5, 10.9, 11.5,11.9, 13.4, 15.8, 16.0, 16.4, 16.6, 17.3, 17.6, 18.2, 18.5, 18.7, 19.4,19.6, 19.8, 20.6, 21.2, 21.4, 21.9, 22.7, 23.1, 23.4, 23.9, 24.5, 24.8,25.0, 26.1, 26.3, 27.0, 27.6, 28.0, 28.5, 28.8, 29.1, 29.5, 29.9, 30.3,31.0, 31.0, 31.5, 32.0, 32.4, 33.1, 33.5, 34.2, and 34.7. One embodimentof the disclosure provides for a crystalline Form D of AP1189 fumarateexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 8.6±0.2, 9.2±0.2, 10.2±0.2, 10.5±0.2, 10.9±0.2,11.5±0.2, 11.9±0.2, 13.4±0.2, 15.8±0.2, 16.0±0.2, 16.4±0.2, 16.6±0.2,17.3±0.2, 17.6±0.2, 18.2±0.2, 18.5±0.2, 18.7±0.2, 19.4±0.2, 19.6±0.2,19.8±0.2, 20.6±0.2, 21.2±0.2, 21.4±0.2, 21.9±0.2, 22.7±0.2, 23.1±0.2,23.4±0.2, 23.9±0.2, 24.5±0.2, 24.8±0.2, 25.0±0.2, 26.1±0.2, 26.3±0.2,27.0±0.2, 27.6±0.2, 28.0±0.2, 28.5±0.2, 28.8±0.2, 29.1±0.2, 29.5±0.2,29.9±0.2, 30.3±0.2, 31.0±0.2, 31.0±0.2, 31.5±0.2, 32.0±0.2, 32.4±0.2,33.1±0.2, 33.5±0.2, 34.2±0.2, and 34.7±0.2. It may be advantageous toidentify the crystalline Form D of AP1189 fumarate by X-ray lines(2-theta values) having a high relative intensity, and/or bycharacteristic X-ray lines. Thus, one embodiment of the presentdisclosure provides for a crystalline Form D of AP1189 fumarateexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 9.2, 10.5, 10.9, 11.5, 11.9, 15.8, 17.6, 18.7,19.4, 21.2, 21.9, 23.4, 23.9, 24.5, 26.3. One embodiment of the presentdisclosure provides for a crystalline Form D of AP1189 fumarateexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 9.2±0.2, 10.5±0.2, 10.9±0.2, 11.5±0.2, 11.9±0.2,15.8±0.2, 17.6±0.2, 18.7±0.2, 19.4±0.2, 21.2±0.2, 21.9±0.2, 23.4±0.2,23.9±0.2, 24.5±0.2, 26.3±0.2. One embodiment of the present disclosureprovides for a crystalline Form D of AP1189 fumarate exhibiting one ormore X-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting ofthe 2-theta values in listed in Table 6.

AP1189 Napadisylate Form III

The present disclosure provides for a crystalline Form III of AP1189napadisylate. Crystalline Form III of AP1189 napadisylate exhibits anXRPD diffractogram as shown in FIG. 14 . One embodiment of the presentdisclosure provides for a crystalline Form III of AP1189 napadisylateexhibiting at least X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation at 13.4±0.2, 22.2±0.2,and 26.8±0.2. One embodiment provides for a crystalline Form III ofAP1189 napadisylate further exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 15.1±0.2, 15.5±0.2,23.5±0.2, and 28.0±0.2. One embodiment of the present disclosureprovides for a crystalline Form III of AP1189 napadisylate furtherexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 7.6±0.2, 10.7±0.2, 12.4±0.2, and 22.8±0.2. Oneembodiment of the disclosure provides for a crystalline Form III ofAP1189 napadisylate exhibiting an X-ray pattern (2-theta values) in apowder diffraction when measured using Cu K_(α) radiation according toFIG. 14 .

One embodiment of the disclosure provides for a crystalline Form III ofAP1189 napadisylate exhibiting one or more X-ray lines (2-theta values)in a powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 7.5, 10.7, 12.4, 13.4, 14.0, 15.1,15.5, 17.2, 18.3, 18.8, 19.3, 20.3, 21.4, 21.8, 22.2, 22.8, 23.5, 24.3,24.9, 25.3, 26.8, 27.1, 27.6, 28.0, 28.5, 28.9, 29.5, 29.9, 30.5, 31.4,31.9, 32.6, and 33.5. embodiment of the disclosure provides for acrystalline Form III of AP1189 napadisylate exhibiting one or more X-raylines (2-theta values) in a powder diffraction pattern when measuredusing Cu K_(α) radiation selected from the group consisting of 7.5±0.2,10.7±0.2, 12.4±0.2, 13.4±0.2, 14.0±0.2, 15.1±0.2, 15.5±0.2, 17.2±0.2,18.3±0.2, 18.8±0.2, 19.3±0.2, 20.3±0.2, 21.4±0.2, 21.8±0.2, 22.2±0.2,22.8±0.2, 23.5±0.2, 24.3±0.2, 24.9±0.2, 25.3±0.2, 26.8±0.2, 27.1±0.2,27.6±0.2, 28.0±0.2, 28.5±0.2, 28.9±0.2, 29.5±0.2, 29.9±0.2, 30.5±0.2,31.4±0.2, 31.9±0.2, 32.6±0.2, and 33.5±0.2. It may be advantageous toidentify the crystalline Form III of AP1189 napadisylate by X-ray lines(2-theta values) having a high relative intensity, and/or bycharacteristic X-ray lines. Thus, one embodiment of the presentdisclosure provides for a crystalline Form III of AP1189 napadisylateexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 7.6, 10.7, 12.4, 13.4, 15.1, 15.5, 22.2, 22.8,23.5, 26.8, and 28.0. One embodiment of the present disclosure providesfor a crystalline Form III of AP1189 napadisylate exhibiting one or moreX-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of7.6±0.2, 10.7±0.2, 12.4±0.2, 13.4±0.2, 15.1±0.2, 15.5±0.2, 22.2±0.2,22.8±0.2, 23.5±0.2, 26.8±0.2, and 28.0±0.2. One embodiment of thepresent disclosure provides for a crystalline Form III of AP1189napadisylate exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of the 2-theta values in listed inTable 9.

AP1189 Napadisylate Form IV

The present disclosure provides for a crystalline Form IV of AP1189napadisylate. Crystalline Form IV of AP1189 napadisylate exhibits anXRPD diffractogram as shown in FIG. 15 . One embodiment of the presentdisclosure provides for a crystalline Form IV of AP1189 napadisylateexhibiting at least X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation at 5.4±0.2, 15.6±0.2, and23.4±0.2. One embodiment provides for a crystalline Form IV of AP1189napadisylate further exhibiting one or more X-ray lines (2-theta values)in a powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 18.4±0.2, 22.0 0.2, 24.2±0.2, and25.8±0.2. One embodiment of the present disclosure provides for acrystalline Form IV of AP1189 napadisylate further exhibiting one ormore X-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of8.5±0.2, 10.8±0.2, 12.6±0.2, 13.1±0.2, 19.5±0.2, 19.9±0.2, 21.1±0.2,22.7±0.2, and 25.2±0.2. One embodiment of the disclosure provides for acrystalline Form IV of AP1189 napadisylate exhibiting an X-ray pattern(2-theta values) in a powder diffraction when measured using Cu K_(α)radiation according to FIG. 15 .

One embodiment of the disclosure provides for a crystalline Form IV ofAP1189 napadisylate exhibiting one or more X-ray lines (2-theta values)in a powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 5.4, 6.5, 7.4, 8.5, 10.1, 10.8,11.3, 12.1, 12.6, 13.1, 15.6, 16.3, 16.6, 18.4, 19.0, 19.5, 19.9, 20.3,21.1, 22.0, 22.7, 23.4, 24.2, 25.2, 25.8, 26.9, and 30.5. One embodimentof the disclosure provides for a crystalline Form IV of AP1189napadisylate exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 5.4±0.2, 6.5±0.2, 7.4±0.2,8.5±0.2, 10.1±0.2, 10.8±0.2, 11.3±0.2, 12.1±0.2, 12.6±0.2, 13.1±0.2,15.6±0.2, 16.3±0.2, 16.6±0.2, 18.4±0.2, 19.0±0.2, 19.5±0.2, 19.9±0.2,20.3±0.2, 21.1±0.2, 22.0±0.2, 22.7±0.2, 23.4±0.2, 24.2±0.2, 25.2±0.2,25.8±0.2, 26.9±0.2, and 30.5±0.2. It may be advantageous to identify thecrystalline Form IV of AP1189 napadisylate by X-ray lines (2-thetavalues) having a high relative intensity, and/or by characteristic X-raylines. Thus, one embodiment of the present disclosure provides for acrystalline Form IV of AP1189 napadisylate exhibiting one or more X-raylines (2-theta values) in a powder diffraction pattern when measuredusing Cu K_(α) radiation selected from the group consisting of 5.4, 8.5,10.8, 12.6, 13.1, 15.6, 18.4, 19.5, 19.9, 21.1, 22.0, 22.7, 23.4, 24.2,25.2, and 25.8. One embodiment of the present disclosure provides for acrystalline Form IV of AP1189 napadisylate exhibiting one or more X-raylines (2-theta values) in a powder diffraction pattern when measuredusing Cu K_(α) radiation selected from the group consisting of 5.4±0.2,8.5±0.2, 10.8±0.2, 12.6±0.2, 13.1±0.2, 15.6±0.2, 18.4±0.2, 19.5±0.2,19.9±0.2, 21.1±0.2, 22.0±0.2, 22.7±0.2, 23.4±0.2, 24.2±0.2, 25.2±0.2,and 25.8±0.2. One embodiment of the present disclosure provides for acrystalline Form IV of AP1189 napadisylate exhibiting one or more X-raylines (2-theta values) in a powder diffraction pattern when measuredusing Cu K_(α) radiation selected from the group consisting of the2-theta values in listed in Table 10.

AP1189 Esylate Form V

The present disclosure provides for a crystalline Form V of AP1189esylate. Crystalline Form V of AP1189 esylate exhibits an XRPDdiffractogram as shown in FIG. 16 . One embodiment of the presentdisclosure provides for a crystalline Form V of AP1189 esylateexhibiting at least X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation at 14.5±0.2, 16.5±0.2,and 18.6±0.2. One embodiment provides for a crystalline Form V of AP1189esylate further exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 9.8±0.2, 19.7±0.2, 20.1±0.2, and26.8±0.2. One embodiment of the present disclosure provides for acrystalline Form V of AP1189 esylate further exhibiting one or moreX-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of8.5±0.2, 10.4±0.2, 15.3±0.2, 21.9±0.2, 22.5±0.2, and 26.1±0.2. Oneembodiment of the disclosure provides for a crystalline Form V of AP1189esylate exhibiting an X-ray pattern (2-theta values) in a powderdiffraction when measured using Cu K_(α) radiation according to FIG. 16.

One embodiment of the disclosure provides for a crystalline Form V ofAP1189 esylate exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 8.5, 9.8, 10.4, 11.3, 11.5, 13.0,14.3, 14.5, 15.3, 16.5, 18.6, 19.7, 20.1, 21.0, 21.1, 21.9, 22.4, 23.9,25.5, 26.1, 26.4, 26.8, 27.5, 29.7, 31.4, 32.2, and 33.5. One embodimentof the disclosure provides for a crystalline Form V of AP1189 esylateexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 8.5±0.2, 9.8±0.2, 10.4±0.2, 11.3±0.2, 11.5±0.2,13.0±0.2, 14.3±0.2, 14.5±0.2, 15.3±0.2, 16.5±0.2, 18.6±0.2, 19.7±0.2,20.1±0.2, 21.0±0.2, 21.1±0.2, 21.9±0.2, 22.4±0.2, 23.9±0.2, 25.5±0.2,26.1±0.2, 26.4±0.2, 26.8±0.2, 27.5±0.2, 29.7±0.2, 31.4±0.2, 32.2±0.2,and 33.5±0.2. It may be advantageous to identify the crystalline Form Vof AP1189 esylate by X-ray lines (2-theta values) having a high relativeintensity, and/or by characteristic X-ray lines. Thus, one embodiment ofthe present disclosure provides for a crystalline Form V of AP1189esylate exhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 8.5, 9.8, 10.4, 14.5, 15.3, 16.5, 18.6, 19.7,20.1, 21.9, 22.5, 26.1, and 26.8. One embodiment of the presentdisclosure provides for a crystalline Form V of AP1189 esylateexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 8.5±0.2, 9.8±0.2, 10.4±0.2, 14.5±0.2, 15.3±0.2,16.5±0.2, 18.6±0.2, 19.7±0.2, 20.1±0.2, 21.9±0.2, 22.5±0.2, 26.1±0.2,and 26.8±0.2. One embodiment of the present disclosure provides for acrystalline Form V of AP1189 esylate exhibiting one or more X-ray lines(2-theta values) in a powder diffraction pattern when measured using CuK_(α) radiation selected from the group consisting of the 2-theta valuesin listed in Table 11.

AP1189 Edisylate Form VI

The present disclosure provides for a crystalline Form VI of AP1189edisylate. Crystalline Form VI of AP1189 edisylate exhibits an XRPDdiffractogram as shown in FIG. 17 . One embodiment of the presentdisclosure provides for a crystalline Form VI of AP1189 edisylateexhibiting at least X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation at 4.8±0.2, 12.8±0.2, and16.5±0.2. One embodiment provides for a crystalline Form VI of AP1189edisylate further exhibiting one or more X-ray lines (2-theta values) ina powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 17.9±0.2, 21.4±0.2, 23.4±0.2, and27.1±0.2. One embodiment of the present disclosure provides for acrystalline Form VI of AP1189 edisylate further exhibiting one or moreX-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of9.5±0.2, 10.9±0.2, 14.3±0.2, 15.2±0.2, 18.6±0.2, and 24.5±0.2. Oneembodiment of the disclosure provides for a crystalline Form VI ofAP1189 edisylate exhibiting an X-ray pattern (2-theta values) in apowder diffraction when measured using Cu K_(α) radiation according toFIG. 17 .

One embodiment of the disclosure provides for a crystalline Form VI ofAP1189 edisylate exhibiting one or more X-ray lines (2-theta values) ina powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 4.8, 9.5, 10.9, 11.6, 12.8, 14.3,15.2, 16.5, 17.0, 17.9, 18.6, 19.2, 20.3, 21.4, 22.5, 23.4, 24.5, 25.3,25.5, 26.5, 27.2, 28.0, 29.5, 29.7, 30.2, 31.0, 32.6, 33.3, and 34.3.One embodiment of the disclosure provides for a crystalline Form VI ofAP1189 edisylate exhibiting one or more X-ray lines (2-theta values) ina powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 4.8±0.2, 9.5±0.2, 10.9±0.2,11.6±0.2, 12.8±0.2, 14.3±0.2, 15.2±0.2, 16.5±0.2, 17.0±0.2, 17.9±0.2,18.6±0.2, 19.2±0.2, 20.3±0.2, 21.4±0.2, 22.5±0.2, 23.4±0.2, 24.5±0.2,25.3±0.2, 25.5±0.2, 26.5±0.2, 27.2±0.2, 28.0±0.2, 29.5±0.2, 29.7±0.2,30.2±0.2, 31.0±0.2, 32.6±0.2, 33.3±0.2, and 34.3±0.2. It may beadvantageous to identify the crystalline Form VI of AP1189 edisylate byX-ray lines (2-theta values) having a high relative intensity, and/or bycharacteristic X-ray lines. Thus, one embodiment of the presentdisclosure provides for a crystalline Form VI of AP1189 edisylateexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 4.8, 9.5, 10.9, 12.8, 14.3, 15.2, 16.5, 17.9,18.6, 21.4, 23.4, 24.5, and 27.1. One embodiment of the presentdisclosure provides for a crystalline Form VI of AP1189 edisylateexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 4.8±0.2, 9.5±0.2, 10.9±0.2, 12.8±0.2, 14.3±0.2,15.2±0.2, 16.5±0.2, 17.9±0.2, 18.6±0.2, 21.4±0.2, 23.4±0.2, 24.5±0.2,and 27.1±0.2. One embodiment of the present disclosure provides for acrystalline Form VI of AP1189 edisylate exhibiting one or more X-raylines (2-theta values) in a powder diffraction pattern when measuredusing Cu K_(α) radiation selected from the group consisting of the2-theta values in listed in Table 12.

AP1189 Edisylate Form VII

The present disclosure provides for a crystalline Form VII of AP1189edisylate. Crystalline Form VII of AP1189 edisylate exhibits an XRPDdiffractogram as shown in FIG. 18 . One embodiment of the presentdisclosure provides for a crystalline Form VII of AP1189 edisylateexhibiting at least X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation at 6.1±0.2, 15.7±0.2, and23.6±0.2. One embodiment provides for a crystalline Form VII of AP1189edisylate further exhibiting one or more X-ray lines (2-theta values) ina powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 12.1, 20.1±0.2, and 21.8±0.2. Oneembodiment of the present disclosure provides for a crystalline Form VIIof AP1189 edisylate further exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 11.7±0.2, 12.7±0.2, and19.3±0.2. One embodiment of the disclosure provides for a crystallineForm VII of AP1189 edisylate exhibiting an X-ray pattern (2-thetavalues) in a powder diffraction when measured using Cu K_(α) radiationaccording to FIG. 18 .

One embodiment of the disclosure provides for a crystalline Form VII ofAP1189 edisylate exhibiting one or more X-ray lines (2-theta values) ina powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 6.1, 10.0, 11.7, 12.1, 12.7, 14.1,15.7, 16.3, 17.6, 17.9, 18.3, 19.3, 20.1, 20.9, 21.8, 22.4, 22.7, 23.6,24.3, 24.8, 25.1, 25.8, 26.5, 27.0, 27.5, 28.2, 28.6, 29.7, 30.6, 31.2,31.9, 32.4, 32.9, 33.5, and 34.1. One embodiment of the disclosureprovides for a crystalline Form VII of AP1189 edisylate exhibiting oneor more X-ray lines (2-theta values) in a powder diffraction patternwhen measured using Cu K_(α) radiation selected from the groupconsisting of 6.1±0.2, 10.0±0.2, 11.7±0.2, 12.1±0.2, 12.7±0.2, 14.1±0.2,15.7±0.2, 16.3±0.2, 17.6±0.2, 17.9±0.2, 18.3±0.2, 19.3±0.2, 20.1±0.2,20.9±0.2, 21.8±0.2, 22.4±0.2, 22.7±0.2, 23.6±0.2, 24.3±0.2, 24.8±0.2,25.1±0.2, 25.8±0.2, 26.5±0.2, 27.0±0.2, 27.5±0.2, 28.2±0.2, 28.6±0.2,29.7±0.2, 30.6±0.2, 31.2±0.2, 31.9±0.2, 32.4±0.2, 32.9±0.2, 33.5±0.2,and 34.1±0.2. It may be advantageous to identify the crystalline FormVII of AP1189 edisylate by X-ray lines (2-theta values) having a highrelative intensity, and/or by characteristic X-ray lines. Thus, oneembodiment of the present disclosure provides for a crystalline Form VIIof AP1189 edisylate exhibiting one or more X-ray lines (2-theta values)in a powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 6.1, 11.7, 12.1, 12.7, 15.7, 19.3,20.1, 21.8, and 23.6. One embodiment of the present disclosure providesfor a crystalline Form VII of AP1189 edisylate exhibiting one or moreX-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of6.1±0.2, 11.7±0.2, 12.1±0.2, 12.7±0.2, 15.7±0.2, 19.3±0.2, 20.1±0.2,21.8±0.2, and 23.6±0.2. One embodiment of the present disclosureprovides for a crystalline Form VII of AP1189 edisylate exhibiting oneor more X-ray lines (2-theta values) in a powder diffraction patternwhen measured using Cu K_(α) radiation selected from the groupconsisting of the 2-theta values in listed in Table 13.

AP1189 Edisylate Form VIII

The present disclosure provides for a crystalline Form VIII of AP1189edisylate. Crystalline Form VIII of AP1189 edisylate exhibits an XRPDdiffractogram as shown in FIG. 19 . One embodiment of the presentdisclosure provides for a crystalline Form VIII of AP1189 edisylateexhibiting at least X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation at 15.5±0.2, 20.7±0.2,and 21.7±0.2. One embodiment provides for a crystalline Form VIII ofAP1189 edisylate further exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 12.1±0.2, 13.0±0.2, and24.1±0.2. One embodiment of the present disclosure provides for acrystalline Form VIII of AP1189 edisylate further exhibiting one or moreX-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of6.4±0.2 and 25.2±0.2. One embodiment of the disclosure provides for acrystalline Form VIII of AP1189 edisylate exhibiting an X-ray pattern(2-theta values) in a powder diffraction when measured using Cu K_(α)radiation according to FIG. 19 .

One embodiment of the disclosure provides for a crystalline Form VIII ofAP1189 edisylate exhibiting one or more X-ray lines (2-theta values) ina powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 6.4, 9.9, 12.1, 12.5, 13.0, 14.0,15.5, 17.8, 18.3, 18.7, 19.5, 20.0, 20.7, 21.7, 22.2, 23.1, 24.1, 25.2,25.7, 27.1, 27.9, 30.7, 31.1, 31.6, and 34.5. One embodiment of thedisclosure provides for a crystalline Form VIII of AP1189 edisylateexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 6.4±0.2, 9.9±0.2, 12.1±0.2, 12.5±0.2, 13.0±0.2,14.0±0.2, 15.5±0.2, 17.8±0.2, 18.3±0.2, 18.7±0.2, 19.5±0.2, 20.0±0.2,20.7±0.2, 21.7±0.2, 22.2±0.2, 23.1±0.2, 24.1±0.2, 25.2±0.2, 25.7±0.2,27.1±0.2, 27.9±0.2, 30.7±0.2, 31.1±0.2, 31.6±0.2, and 34.5±0.2. It maybe advantageous to identify the crystalline Form VIII of AP1189edisylate by X-ray lines (2-theta values) having a high relativeintensity, and/or by characteristic X-ray lines. Thus, one embodiment ofthe present disclosure provides for a crystalline Form VIII of AP1189edisylate exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 6.4, 12.1, 13.0, 15.5, 20.7, 21.7,24.1, and 25.2. One embodiment of the present disclosure provides for acrystalline Form VIII of AP1189 edisylate exhibiting one or more X-raylines (2-theta values) in a powder diffraction pattern when measuredusing Cu K_(α) radiation selected from the group consisting of 6.4±0.2,12.1±0.2, 13.0±0.2, 15.5±0.2, 20.7±0.2, 21.7±0.2, 24.1±0.2, and25.2±0.2. One embodiment of the present disclosure provides for acrystalline Form VIII of AP1189 edisylate exhibiting one or more X-raylines (2-theta values) in a powder diffraction pattern when measuredusing Cu K_(α) radiation selected from the group consisting of the2-theta values in listed in Table 14.

AP1189 Edisylate Form IX

The present disclosure provides for a crystalline Form IX of AP1189edisylate. Crystalline Form IX of AP1189 edisylate exhibits an XRPDdiffractogram as shown in FIG. 20 . One embodiment of the presentdisclosure provides for a crystalline Form IX of AP1189 edisylateexhibiting at least X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation at 4.5±0.2, 16.7±0.2, and24.7±0.2. One embodiment provides for a crystalline Form IX of AP1189edisylate further exhibiting one or more X-ray lines (2-theta values) ina powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 12.2±0.2 and 15.5±0.2. Oneembodiment of the present disclosure provides for a crystalline Form IXof AP1189 edisylate further exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 9.0±0.2 and 18.0. Oneembodiment of the disclosure provides for a crystalline Form IX ofAP1189 edisylate exhibiting an X-ray pattern (2-theta values) in apowder diffraction when measured using Cu K_(α) radiation according toFIG. 20 .

One embodiment of the disclosure provides for a crystalline Form IX ofAP1189 edisylate exhibiting one or more X-ray lines (2-theta values) ina powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 4.5, 9.0, 11.7, 12.2, 12.4, 13.1,15.5, 16.7, 17.3, 18.0, 19.9, 20.4, 21.1, 22.0, 22.9, 24.7, 26.8, and28.3. One embodiment of the disclosure provides for a crystalline FormIX of AP1189 edisylate exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 4.5±0.2, 9.0±0.2,11.7±0.2, 12.2±0.2, 12.4±0.2, 13.1±0.2, 15.5±0.2, 16.7±0.2, 17.3±0.2,18.0±0.2, 19.9±0.2, 20.4±0.2, 21.1±0.2, 22.0±0.2, 22.9±0.2, 24.7±0.2,26.8±0.2, and 28.3±0.2. It may be advantageous to identify thecrystalline Form IX of AP1189 edisylate by X-ray lines (2-theta values)having a high relative intensity, and/or by characteristic X-ray lines.Thus, one embodiment of the present disclosure provides for acrystalline Form IX of AP1189 edisylate exhibiting one or more X-raylines (2-theta values) in a powder diffraction pattern when measuredusing Cu K_(α) radiation selected from the group consisting of 4.5, 9.0,12.2, 15.5, 16.7, 18.0, and 24.7. One embodiment of the presentdisclosure provides for a crystalline Form IX of AP1189 edisylateexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 4.5±0.2, 9.0±0.2, 12.2±0.2, 15.5±0.2, 16.7±0.2,18.0±0.2, and 24.7±0.2. One embodiment of the present disclosureprovides for a crystalline Form IX of AP1189 edisylate exhibiting one ormore X-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting ofthe 2-theta values in listed in Table 15.

AP1189 Nitrate Form X

The present disclosure provides for a crystalline Form X of AP1189nitrate. Crystalline Form X of AP1189 nitrate exhibits an XRPDdiffractogram as shown in FIG. 21 . One embodiment of the presentdisclosure provides for a crystalline Form X of AP1189 nitrateexhibiting at least X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation at 15.3±0.2, 21.4±0.2,and 25.1±0.2. One embodiment provides for a crystalline Form X of AP1189nitrate further exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 11.9±0.2, 12.5±0.2, and 27.7±0.2.One embodiment of the present disclosure provides for a crystalline FormX of AP1189 nitrate further exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 3.7±0.2, 7.5±0.2,14.7±0.2, 17.7±0.2, and 18.1±0.2. One embodiment of the disclosureprovides for a crystalline Form X of AP1189 nitrate exhibiting an X-raypattern (2-theta values) in a powder diffraction when measured using CuK_(α) radiation according to FIG. 21 .

One embodiment of the disclosure provides for a crystalline Form X ofAP1189 nitrate exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 3.7, 7.5, 11.9, 12.5, 13.1, 14.7,15.3, 16.9, 17.7, 18.1, 18.7, 19.6, 21.4, 23.0, 24.1, 25.1, 26.6, 27.7,29.5, and 31.7. One embodiment of the disclosure provides for acrystalline Form X of AP1189 nitrate exhibiting one or more X-ray lines(2-theta values) in a powder diffraction pattern when measured using CuK_(α) radiation selected from the group consisting of 3.7±0.2, 7.5±0.2,11.9±0.2, 12.5±0.2, 13.1±0.2, 14.7±0.2, 15.3±0.2, 16.9±0.2, 17.7±0.2,18.1±0.2, 18.7±0.2, 19.6±0.2, 21.4±0.2, 23.0±0.2, 24.1±0.2, 25.1±0.2,26.6±0.2, 27.7±0.2, 29.5±0.2, and 31.7±0.2. It may be advantageous toidentify the crystalline Form X of AP1189 nitrate by X-ray lines(2-theta values) having a high relative intensity, and/or bycharacteristic X-ray lines. Thus, one embodiment of the presentdisclosure provides for a crystalline Form X of AP1189 nitrateexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 3.7, 7.5, 11.9, 12.5, 14.7, 15.3, 17.7, 18.1,21.4, 25.1, and 27.7. One embodiment of the present disclosure providesfor a crystalline Form X of AP1189 nitrate exhibiting one or more X-raylines (2-theta values) in a powder diffraction pattern when measuredusing Cu K_(α) radiation selected from the group consisting of 3.7±0.2,7.5±0.2, 11.9±0.2, 12.5±0.2, 14.7±0.2, 15.3±0.2, 17.7±0.2, 18.1±0.2,21.4±0.2, 25.1±0.2, and 27.7±0.2. One embodiment of the presentdisclosure provides for a crystalline Form X of AP1189 nitrateexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of the 2-theta values in listed in Table 16.

AP1189 Cyclamate Form XI

The present disclosure provides for a crystalline Form XI of AP1189cyclamate. Crystalline Form XI of AP1189 cyclamate exhibits an XRPDdiffractogram as shown in FIG. 22 . One embodiment of the presentdisclosure provides for a crystalline Form XI of AP1189 cyclamateexhibiting at least X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation at 7.0±0.2, 13.8±0.2, and15.7±0.2. One embodiment provides for a crystalline Form XI of AP1189cyclamate further exhibiting one or more X-ray lines (2-theta values) ina powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 15.3±0.2, 20.7±0.2, and 21.5±0.2.One embodiment of the present disclosure provides for a crystalline FormXI of AP1189 cyclamate further exhibiting one or more X-ray lines(2-theta values) in a powder diffraction pattern when measured using CuK_(α) radiation selected from the group consisting of 3.2±0.2, 11.3±0.2,and 21.8±0.2. One embodiment of the disclosure provides for acrystalline Form XI of AP1189 cyclamate exhibiting an X-ray pattern(2-theta values) in a powder diffraction when measured using Cu K_(α)radiation according to FIG. 22 .

One embodiment of the disclosure provides for a crystalline Form XI ofAP1189 cyclamate exhibiting one or more X-ray lines (2-theta values) ina powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 3.2, 5.2, 7.0, 10.4, 11.3, 11.9,13.8, 14.2, 15.3, 15.7, 16.3, 17.6, 18.5, 19.2, 20.1, 20.7, 21.5, 21.8,22.1, 22.7, 23.4, 25.2, 26.0, and 27.8. One embodiment of the disclosureprovides for a crystalline Form XI of AP1189 cyclamate exhibiting one ormore X-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of3.2±0.2, 5.2±0.2, 7.0±0.2, 10.4±0.2, 11.3±0.2, 11.9±0.2, 13.8±0.2,14.2±0.2, 15.3±0.2, 15.7±0.2, 16.3±0.2, 17.6±0.2, 18.5±0.2, 19.2±0.2,20.1±0.2, 20.7±0.2, 21.5±0.2, 21.8±0.2, 22.1±0.2, 22.7±0.2, 23.4±0.2,25.2±0.2, 26.0±0.2, and 27.8±0.2. It may be advantageous to identify thecrystalline Form XI of AP1189 cyclamate by X-ray lines (2-theta values)having a high relative intensity, and/or by characteristic X-ray lines.Thus, one embodiment of the present disclosure provides for acrystalline Form XI of AP1189 cyclamate exhibiting one or more X-raylines (2-theta values) in a powder diffraction pattern when measuredusing Cu K_(α) radiation selected from the group consisting of 3.2, 7.0,11.3, 13.8, 15.3, 15.7, 20.7, 21.5, and 21.8. One embodiment of thepresent disclosure provides for a crystalline Form XI of AP1189cyclamate exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 3.2±0.2, 7.0±0.2, 11.3±0.2,13.8±0.2, 15.3±0.2, 15.7±0.2, 20.7±0.2, 21.5±0.2, and 21.8±0.2. Oneembodiment of the present disclosure provides for a crystalline Form XIof AP1189 cyclamate exhibiting one or more X-ray lines (2-theta values)in a powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of the 2-theta values in listed inTable 17.

AP1189 Cyclamate Form XII

The present disclosure provides for a crystalline Form XII of AP1189cyclamate. Crystalline Form XII of AP1189 cyclamate exhibits an XRPDdiffractogram as shown in FIG. 23 . One embodiment of the presentdisclosure provides for a crystalline Form XII of AP1189 cyclamateexhibiting at least X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation at 7.3±0.2, 15.3±0.2, and17.9±0.2. One embodiment provides for a crystalline Form XII of AP1189cyclamate further exhibiting one or more X-ray lines (2-theta values) ina powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 16.3±0.2, 19.1±0.2, 22.0 0.2, and22.7±0.2. One embodiment of the present disclosure provides for acrystalline Form XII of AP1189 cyclamate further exhibiting one or moreX-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of11.3±0.2, 13.1±0.2, and 16.9±0.2. One embodiment of the disclosureprovides for a crystalline Form XII of AP1189 cyclamate exhibiting anX-ray pattern (2-theta values) in a powder diffraction when measuredusing Cu K_(α) radiation according to FIG. 23 .

One embodiment of the disclosure provides for a crystalline Form XII ofAP1189 cyclamate exhibiting one or more X-ray lines (2-theta values) ina powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 6.3, 7.3, 9.3, 11.3, 12.7, 13.1,14.8, 15.3, 16.3, 16.9, 17.9, 19.1, 19.3, 20.1, 22.0, 22.7, 24.1, 24.8,25.8, 27.1, 28.0, and 29.0. One embodiment of the disclosure providesfor a crystalline Form XII of AP1189 cyclamate exhibiting one or moreX-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of6.3±0.2, 7.3±0.2, 9.3±0.2, 11.3±0.2, 12.7±0.2, 13.1±0.2, 14.8±0.2,15.3±0.2, 16.3±0.2, 16.9±0.2, 17.9±0.2, 19.1±0.2, 19.3±0.2, 20.1±0.2,22.0±0.2, 22.7±0.2, 24.1±0.2, 24.8±0.2, 25.8±0.2, 27.1±0.2, 28.0±0.2,and 29.0±0.2. It may be advantageous to identify the crystalline FormXII of AP1189 cyclamate by X-ray lines (2-theta values) having a highrelative intensity, and/or by characteristic X-ray lines. Thus, oneembodiment of the present disclosure provides for a crystalline Form XIIof AP1189 cyclamate exhibiting one or more X-ray lines (2-theta values)in a powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 7.3, 11.3, 13.1, 14.3, 16.3, 16.9,17.9, 19.1, 22.0, and 22.7. One embodiment of the present disclosureprovides for a crystalline Form XII of AP1189 cyclamate exhibiting oneor more X-ray lines (2-theta values) in a powder diffraction patternwhen measured using Cu K_(α) radiation selected from the groupconsisting of 7.3±0.2, 11.3±0.2, 13.1±0.2, 14.3±0.2, 16.3±0.2, 16.9±0.2,17.9±0.2, 19.1±0.2, 22.0±0.2, and 22.7±0.2. One embodiment of thepresent disclosure provides for a crystalline Form XII of AP1189cyclamate exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of the 2-theta values in listed inTable 18.

AP1189 Cyclamate Form XIII

The present disclosure provides for a crystalline Form XIII of AP1189cyclamate. Crystalline Form XIII of AP1189 cyclamate exhibits an XRPDdiffractogram as shown in FIG. 24 . One embodiment of the presentdisclosure provides for a crystalline Form XIII of AP1189 cyclamateexhibiting at least X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation at 15.3±0.2, 18.5±0.2,and 18.7±0.2. One embodiment provides for a crystalline Form XIII ofAP1189 cyclamate further exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 6.4±0.2, 14.6±0.2,16.7±0.2, and 19.8±0.2. One embodiment of the present disclosureprovides for a crystalline Form XIII of AP1189 cyclamate furtherexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 5.6±0.2, 7.1±0.2, 8.5±0.2, 10.5±0.2, 13.1±0.2,and 16.2±0.2. One embodiment of the disclosure provides for acrystalline Form XIII of AP1189 cyclamate exhibiting an X-ray pattern(2-theta values) in a powder diffraction when measured using Cu K_(α)radiation according to FIG. 24 .

One embodiment of the disclosure provides for a crystalline Form XIII ofAP1189 cyclamate exhibiting one or more X-ray lines (2-theta values) ina powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 3.3, 5.6, 6.4, 7.1, 7.6, 8.5, 9.4,9.9, 10.2, 10.5, 10.9, 11.6, 11.9, 12.3, 13.1, 13.3, 13.7, 14.1, 14.6,15.3, 16.2, 16.7, 17.5, 18.5, 18.7, 19.8, 20.2, 20.6, 21.1, 21.1, 21.3,21.7, 22.1, 22.6, 22.8, 23.7, 24.1, 24.9, 25.1, 25.7, 26.2, 27.0, 27.7,28.7, 29.4, 30.0, 30.8, 31.6, 32.4, and 33.6. One embodiment of thedisclosure provides for a crystalline Form XIII of AP1189 cyclamateexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 3.3±0.2, 5.6±0.2, 6.4±0.2, 7.1±0.2, 7.6±0.2,8.5±0.2, 9.4±0.2, 9.9±0.2, 10.2±0.2, 10.5±0.2, 10.9±0.2, 11.6±0.2,11.9±0.2, 12.3±0.2, 13.1±0.2, 13.3±0.2, 13.7±0.2, 14.1±0.2, 14.6±0.2,15.3±0.2, 16.2±0.2, 16.7±0.2, 17.5±0.2, 18.5±0.2, 18.7±0.2, 19.8±0.2,20.2±0.2, 20.6±0.2, 21.1±0.2, 21.1±0.2, 21.3±0.2, 21.7±0.2, 22.1±0.2,22.6±0.2, 22.8±0.2, 23.7±0.2, 24.1±0.2, 24.9±0.2, 25.1±0.2, 25.7±0.2,26.2±0.2, 27.0±0.2, 27.7±0.2, 28.7±0.2, 29.4±0.2, 30.0±0.2, 30.8±0.2,31.6±0.2, 32.4±0.2, and 33.6±0.2. It may be advantageous to identify thecrystalline Form XIII of AP1189 cyclamate by X-ray lines (2-thetavalues) having a high relative intensity, and/or by characteristic X-raylines. Thus, one embodiment of the present disclosure provides for acrystalline Form XIII of AP1189 cyclamate exhibiting one or more X-raylines (2-theta values) in a powder diffraction pattern when measuredusing Cu K_(α) radiation selected from the group consisting of 5.6, 6.4,7.1, 8.5, 10.5, 13.1, 14.6, 15.3, 16.2, 16.7, 18.5, 18.7, 19.8, 26.2,and 27.0. One embodiment of the present disclosure provides for acrystalline Form XIII of AP1189 cyclamate exhibiting one or more X-raylines (2-theta values) in a powder diffraction pattern when measuredusing Cu K_(α) radiation selected from the group consisting of 5.6±0.2,6.4±0.2, 7.1±0.2, 8.5±0.2, 10.5±0.2, 13.1±0.2, 14.6±0.2, 15.3±0.2,16.2±0.2, 16.7±0.2, 18.5±0.2, 18.7±0.2, 19.8±0.2, 26.2±0.2, and27.0±0.2. One embodiment of the present disclosure provides for acrystalline Form XIII of AP1189 cyclamate exhibiting one or more X-raylines (2-theta values) in a powder diffraction pattern when measuredusing Cu K_(α) radiation selected from the group consisting of the2-theta values in listed in Table 19.

AP1189 Besylate Form XIV

The present disclosure provides for a crystalline Form XIV of AP1189besylate. Crystalline Form XIV of AP1189 besylate exhibits an XRPDdiffractogram as shown in FIG. 25 . One embodiment of the presentdisclosure provides for a crystalline Form XIV of AP1189 besylateexhibiting at least X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation at 13.0±0.2, 15.1±0.2,and 19.9±0.2. One embodiment provides for a crystalline Form XIV ofAP1189 besylate further exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 11.2±0.2 and 18.3±0.2.One embodiment of the present disclosure provides for a crystalline FormXIV of AP1189 besylate further exhibiting one or more X-ray lines(2-theta values) in a powder diffraction pattern when measured using CuK_(α) radiation selected from the group consisting of 8.3±0.2, 9.0 0.2,16.4±0.2, and 18.7±0.2. One embodiment of the disclosure provides for acrystalline Form XIV of AP1189 besylate exhibiting an X-ray pattern(2-theta values) in a powder diffraction when measured using Cu K_(α)radiation according to FIG. 25 .

One embodiment of the disclosure provides for a crystalline Form XIV ofAP1189 besylate exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 3.2, 8.3, 9.0, 9.9, 10.8, 11.2,13.0, 13.1, 15.1, 16.0, 16.4, 16.7, 17.3, 18.1, 18.3, 18.7, 19.0, 19.4,19.9, 20.3, 20.9, 21.3, 21.7, 22.0, 22.8, 23.1, 23.6, 24.8, 25.1, 25.4,26.3, 26.5, 27.1, 28.1, 28.5, 29.8, 30.4, 31.1, 32.0, 33.2, and 34.1.One embodiment of the disclosure provides for a crystalline Form XIV ofAP1189 besylate exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 3.2±0.2, 8.3±0.2, 9.0±0.2,9.9±0.2, 10.8±0.2, 11.2±0.2, 13.0±0.2, 13.1±0.2, 15.1±0.2, 16.0±0.2,16.4±0.2, 16.7±0.2, 17.3±0.2, 18.1±0.2, 18.3±0.2, 18.7±0.2, 19.0±0.2,19.4±0.2, 19.9±0.2, 20.3±0.2, 20.9±0.2, 21.3±0.2, 21.7±0.2, 22.0±0.2,22.8±0.2, 23.1±0.2, 23.6±0.2, 24.8±0.2, 25.1±0.2, 25.4±0.2, 26.3±0.2,26.5±0.2, 27.1±0.2, 28.1±0.2, 28.5±0.2, 29.8±0.2, 30.4±0.2, 31.1±0.2,32.0±0.2, 33.2±0.2, and 34.1±0.2. It may be advantageous to identify thecrystalline Form XIV of AP1189 besylate by X-ray lines (2-theta values)having a high relative intensity, and/or by characteristic X-ray lines.Thus, one embodiment of the present disclosure provides for acrystalline Form XIV of AP1189 besylate exhibiting one or more X-raylines (2-theta values) in a powder diffraction pattern when measuredusing Cu K_(α) radiation selected from the group consisting of 8.3, 9.0,11.2, 13.0, 15.1, 16.4, 18.3, 18.7, and 19.9. One embodiment of thepresent disclosure provides for a crystalline Form XIV of AP1189besylate exhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 8.3±0.2, 9.0±0.2, 11.2±0.2, 13.0±0.2, 15.1±0.2,16.4±0.2, 18.3±0.2, 18.7±0.2, and 19.9±0.2. One embodiment of thepresent disclosure provides for a crystalline Form XIV of AP1189besylate exhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of the 2-theta values in listed in Table 20.

AP1189 Oxalate Form XV

The present disclosure provides for a crystalline Form XV of AP1189oxalate. Crystalline Form XV of AP1189 oxalate exhibits an XRPDdiffractogram as shown in FIG. 26 . One embodiment of the presentdisclosure provides for a crystalline Form XV of AP1189 oxalateexhibiting at least X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation at 19.5±0.2, 23.3±0.2,and 25.8±0.2. One embodiment provides for a crystalline Form XV ofAP1189 oxalate further exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 13.9±0.2, 15.6±0.2, and23.8±0.2. One embodiment of the present disclosure provides for acrystalline Form XV of AP1189 oxalate further exhibiting one or moreX-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of7.2±0.2, 10.8±0.2, and 21.7±0.2. One embodiment of the disclosureprovides for a crystalline Form XV of AP1189 oxalate exhibiting an X-raypattern (2-theta values) in a powder diffraction when measured using CuK_(α) radiation according to FIG. 26 .

One embodiment of the disclosure provides for a crystalline Form XV ofAP1189 oxalate exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 7.2, 10.8, 12.1, 13.9, 14.5, 15.0,15.6, 16.5, 16.8, 17.3, 18.2, 18.5, 19.5, 20.1, 21.7, 22.9, 23.3, 23.8,24.3, 24.8, 25.8, 27.0, 27.9, 28.6, 29.3, 29.7, 30.2, 32.2, and 32.9.

One embodiment of the disclosure provides for a crystalline Form XV ofAP1189 oxalate exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 7.2±0.2, 10.8±0.2, 12.1±0.2,13.9±0.2, 14.5±0.2, 15.0±0.2, 15.6±0.2, 16.5±0.2, 16.8±0.2, 17.3±0.2,18.2±0.2, 18.5±0.2, 19.5±0.2, 20.1±0.2, 21.7±0.2, 22.9±0.2, 23.3±0.2,23.8±0.2, 24.3±0.2, 24.8±0.2, 25.8±0.2, 27.0±0.2, 27.9±0.2, 28.6±0.2,29.3±0.2, 29.7±0.2, 30.2±0.2, 32.2±0.2, and 32.9±0.2. It may beadvantageous to identify the crystalline Form XV of AP1189 oxalate byX-ray lines (2-theta values) having a high relative intensity, and/or bycharacteristic X-ray lines. Thus, one embodiment of the presentdisclosure provides for a crystalline Form XV of AP1189 oxalateexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 7.2, 10.8, 13.9, 15.6, 19.5, 21.7, 23.3, 23.8,and 25.8. One embodiment of the present disclosure provides for acrystalline Form XV of AP1189 oxalate exhibiting one or more X-ray lines(2-theta values) in a powder diffraction pattern when measured using CuK_(α) radiation selected from the group consisting of 7.2±0.2, 10.8±0.2,13.9±0.2, 15.6±0.2, 19.5±0.2, 21.7±0.2, 23.3±0.2, 23.8±0.2, and25.8±0.2. One embodiment of the present disclosure provides for acrystalline Form XV of AP1189 oxalate exhibiting one or more X-ray lines(2-theta values) in a powder diffraction pattern when measured using CuK_(α) radiation selected from the group consisting of the 2-theta valuesin listed in Table 21.

AP1189 Oxalate Form XVI

The present disclosure provides for a crystalline Form XVI of AP1189oxalate. Crystalline Form XVI of AP1189 oxalate exhibits an XRPDdiffractogram as shown in FIG. 27 . One embodiment of the presentdisclosure provides for a crystalline Form XVI of AP1189 oxalateexhibiting at least X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation at 17.1±0.2, 17.9±0.2,and 19.6±0.2. One embodiment provides for a crystalline Form XVI ofAP1189 oxalate further exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 15.9±0.2, 24.2±0.2,24.4±0.2, and 27.3±0.2. One embodiment of the present disclosureprovides for a crystalline Form XVI of AP1189 oxalate further exhibitingone or more X-ray lines (2-theta values) in a powder diffraction patternwhen measured using Cu K_(α) radiation selected from the groupconsisting of 9.5±0.2, 11.3±0.2, 21.2±0.2, and 25.4±0.2. One embodimentof the disclosure provides for a crystalline Form XVI of AP1189 oxalateexhibiting an X-ray pattern (2-theta values) in a powder diffractionwhen measured using Cu K_(α) radiation according to FIG. 27 .

One embodiment of the disclosure provides for a crystalline Form XVI ofAP1189 oxalate exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 9.5, 11.3, 12.1, 13.1, 14.0, 15.3,15.9, 16.4, 17.1, 17.9, 18.9, 19.6, 20.0, 21.2, 22.0, 22.7, 23.0, 23.4,24.2, 24.4, 24.8, 25.4, 25.7, 26.3, 27.3, 28.4, 29.9, 30.4, 31.3, 32.2,33.3, 33.9, 34.3, and 34.9. One embodiment of the disclosure providesfor a crystalline Form XVI of AP1189 oxalate exhibiting one or moreX-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of9.5±0.2, 11.3±0.2, 12.1±0.2, 13.1±0.2, 14.0±0.2, 15.3±0.2, 15.9±0.2,16.4±0.2, 17.1±0.2, 17.9±0.2, 18.9±0.2, 19.6±0.2, 20.0±0.2, 21.2±0.2,22.0±0.2, 22.7±0.2, 23.0±0.2, 23.4±0.2, 24.2±0.2, 24.4±0.2, 24.8±0.2,25.4±0.2, 25.7±0.2, 26.3±0.2, 27.3±0.2, 28.4±0.2, 29.9±0.2, 30.4±0.2,31.3±0.2, 32.2±0.2, 33.3±0.2, 33.9±0.2, 34.3±0.2, and 34.9±0.2. It maybe advantageous to identify the crystalline Form XVI of AP1189 oxalateby X-ray lines (2-theta values) having a high relative intensity, and/orby characteristic X-ray lines. Thus, one embodiment of the presentdisclosure provides for a crystalline Form XVI of AP1189 oxalateexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 9.5, 11.3, 15.9, 17.1, 17.9, 19.6, 21.2, 24.2,24.4, 25.4, and 27.3. One embodiment of the present disclosure providesfor a crystalline Form XVI of AP1189 oxalate exhibiting one or moreX-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of9.5±0.2, 11.3±0.2, 15.9±0.2, 17.1±0.2, 17.9±0.2, 19.6±0.2, 21.2±0.2,24.2±0.2, 24.4±0.2, 25.4±0.2, and 27.3±0.2. One embodiment of thepresent disclosure provides for a crystalline Form XVI of AP1189 oxalateexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of the 2-theta values in listed in Table 22.

AP1189 Oxalate Form XVII

The present disclosure provides for a crystalline Form XVII of AP1189oxalate. Crystalline Form XVII of AP1189 oxalate exhibits an XRPDdiffractogram as shown in FIG. 28 . One embodiment of the presentdisclosure provides for a crystalline Form XVII of AP1189 oxalateexhibiting at least X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation at 6.3±0.2, 10.6±0.2, and19.8±0.2. One embodiment provides for a crystalline Form XVII of AP1189oxalate further exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 11.7±0.2, 12.3±0.2, 18.4±0.2, and23.8±0.2. One embodiment of the present disclosure provides for acrystalline Form XVII of AP1189 oxalate further exhibiting one or moreX-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of14.1±0.2, 23.5±0.2, and 30.0±0.2. One embodiment of the disclosureprovides for a crystalline Form XVII of AP1189 oxalate exhibiting anX-ray pattern (2-theta values) in a powder diffraction when measuredusing Cu K_(α) radiation according to FIG. 28 .

One embodiment of the disclosure provides for a crystalline Form XVII ofAP1189 oxalate exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 6.3, 8.2, 10.6, 11.7, 12.3, 12.6,12.9, 13.2, 14.1, 14.2, 15.8, 16.1, 17.1, 17.8, 18.4, 19.0, 19.2, 19.8,20.3, 20.7, 21.0, 21.4, 21.8, 22.0, 22.3, 22.6, 23.2, 23.5, 23.8, 24.4,24.8, 25.4, 25.9, 26.1, 26.6, 27.1, 27.5, 27.8, 28.3, 28.7, 29.0, 30.0,31.1, 33.0, 33.7, and 34.3. One embodiment of the disclosure providesfor a crystalline Form XVII of AP1189 oxalate exhibiting one or moreX-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of6.3±0.2, 8.2±0.2, 10.6±0.2, 11.7±0.2, 12.3±0.2, 12.6±0.2, 12.9±0.2,13.2±0.2, 14.1±0.2, 14.2±0.2, 15.8±0.2, 16.1±0.2, 17.1±0.2, 17.8±0.2,18.4±0.2, 19.0±0.2, 19.2±0.2, 19.8±0.2, 20.3±0.2, 20.7±0.2, 21.0±0.2,21.4±0.2, 21.8±0.2, 22.0±0.2, 22.3±0.2, 22.6±0.2, 23.2±0.2, 23.5±0.2,23.8±0.2, 24.4±0.2, 24.8±0.2, 25.4±0.2, 25.9±0.2, 26.1±0.2, 26.6±0.2,27.1±0.2, 27.5±0.2, 27.8±0.2, 28.3±0.2, 28.7±0.2, 29.0±0.2, 30.0±0.2,31.1±0.2, 33.0±0.2, 33.7±0.2, and 34.3±0.2. It may be advantageous toidentify the crystalline Form XVII of AP1189 oxalate by X-ray lines(2-theta values) having a high relative intensity, and/or bycharacteristic X-ray lines. Thus, one embodiment of the presentdisclosure provides for a crystalline Form XVII of AP1189 oxalateexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 6.3, 10.6, 11.7, 12.3, 14.1, 18.4, 19.8, 23.5,23.8, and 30.0. One embodiment of the present disclosure provides for acrystalline Form XVII of AP1189 oxalate exhibiting one or more X-raylines (2-theta values) in a powder diffraction pattern when measuredusing Cu K_(α) radiation selected from the group consisting of 6.3±0.2,10.6±0.2, 11.7±0.2, 12.3±0.2, 14.1±0.2, 18.4±0.2, 19.8±0.2, 23.5±0.2,23.8±0.2, and 30.0±0.2. One embodiment of the present disclosureprovides for a crystalline Form XVII of AP1189 oxalate exhibiting one ormore X-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting ofthe 2-theta values in listed in Table 23.

AP1189 (+)-Camphor-10-Sulfonic Acid Form XVIII

The present disclosure provides for a crystalline Form XVIII of AP1189(+)-camphor-10-sulfonic acid. Crystalline Form XVIII of AP1189(+)-camphor-10-sulfonic acid exhibits an XRPD diffractogram as shown inFIG. 29 . One embodiment of the present disclosure provides for acrystalline Form XVIII of AP1189 (+)-camphor-10-sulfonic acid exhibitingat least X-ray lines (2-theta values) in a powder diffraction patternwhen measured using Cu K_(α) radiation at 6.5±0.2, 11.5±0.2, and14.8±0.2. One embodiment provides for a crystalline Form XVIII of AP1189(+)-camphor-10-sulfonic acid further exhibiting one or more X-ray lines(2-theta values) in a powder diffraction pattern when measured using CuK_(α) radiation selected from the group consisting of 13.0±0.2,13.7±0.2, 16.1±0.2, and 21.1±0.2. One embodiment of the presentdisclosure provides for a crystalline Form XVIII of AP1189(+)-camphor-10-sulfonic acid further exhibiting one or more X-ray lines(2-theta values) in a powder diffraction pattern when measured using CuK_(α) radiation selected from the group consisting of 15.9±0.2,18.8±0.2, and 19.8±0.2. One embodiment of the disclosure provides for acrystalline Form XVIII of AP1189 (+)-camphor-10-sulfonic acid exhibitingan X-ray pattern (2-theta values) in a powder diffraction when measuredusing Cu K_(α) radiation according to FIG. 29 .

One embodiment of the disclosure provides for a crystalline Form XVIIIof AP1189 (+)-camphor-10-sulfonic acid exhibiting one or more X-raylines (2-theta values) in a powder diffraction pattern when measuredusing Cu K_(α) radiation selected from the group consisting of 5.1, 6.5,7.7, 9.4, 9.9, 10.4, 11.0, 11.5, 12.2, 13.0, 13.7, 14.0, 14.3, 14.8,15.6, 15.9, 16.1, 17.2, 18.1, 18.4, 18.8, 19.8, 21.1, 21.5, 22.2, 22.7,23.2, 23.8, 25.1, 25.7, 26.1, 27.2, 28.7, 30.1, and 31.5. One embodimentof the disclosure provides for a crystalline Form XVIII of AP1189(+)-camphor-10-sulfonic acid exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 5.1±0.2, 6.5±0.2,7.7±0.2, 9.4±0.2, 9.9±0.2, 10.4±0.2, 11.0±0.2, 11.5±0.2, 12.2±0.2,13.0±0.2, 13.7±0.2, 14.0±0.2, 14.3±0.2, 14.8±0.2, 15.6±0.2, 15.9±0.2,16.1±0.2, 17.2±0.2, 18.1±0.2, 18.4±0.2, 18.8±0.2, 19.8±0.2, 21.1±0.2,21.5±0.2, 22.2±0.2, 22.7±0.2, 23.2±0.2, 23.8±0.2, 25.1±0.2, 25.7±0.2,26.1±0.2, 27.2±0.2, 28.7±0.2, 30.1±0.2, and 31.5±0.2. It may beadvantageous to identify the crystalline Form XVIII of AP1189(+)-camphor-10-sulfonic acid by X-ray lines (2-theta values) having ahigh relative intensity, and/or by characteristic X-ray lines. Thus, oneembodiment of the present disclosure provides for a crystalline FormXVIII of AP1189 (+)-camphor-10-sulfonic acid exhibiting one or moreX-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of6.5, 11.5, 13.0, 13.7, 14.8, 15.9, 16.1, 18.8, 19.8, and 21.1. Oneembodiment of the present disclosure provides for a crystalline FormXVIII of AP1189 (+)-camphor-10-sulfonic acid exhibiting one or moreX-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of6.5±0.2, 11.5±0.2, 13.0±0.2, 13.7±0.2, 14.8±0.2, 15.9±0.2, 16.1±0.2,18.8±0.2, 19.8±0.2, and 21.1±0.2. One embodiment of the presentdisclosure provides for a crystalline Form XVIII of AP1189(+)-camphor-10-sulfonic acid exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of the 2-theta values inlisted in Table 24.

AP1189 Oxoglutarate Form XIX

The present disclosure provides for a crystalline Form XIX of AP1189oxoglutarate. Crystalline Form XIX of AP1189 oxoglutarate exhibits anXRPD diffractogram as shown in FIG. 30 . One embodiment of the presentdisclosure provides for a crystalline Form XIX of AP1189 oxoglutarateexhibiting at least X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation at 16.8±0.2, 23.4±0.2,and 23.6±0.2. One embodiment provides for a crystalline Form XIX ofAP1189 oxoglutarate further exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 13.4±0.2, 16.4±0.2,21.6±0.2, and 26.5±0.2. One embodiment of the present disclosureprovides for a crystalline Form XIX of AP1189 oxoglutarate furtherexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 9.1±0.2, 10.7±0.2, 12.8±0.2, 13.2±0.2, 20.8±0.2,24.1±0.2, and 24.2±0.2. One embodiment of the disclosure provides for acrystalline Form XIX of AP1189 oxoglutarate exhibiting an X-ray pattern(2-theta values) in a powder diffraction when measured using Cu K_(α)radiation according to FIG. 30 .

One embodiment of the disclosure provides for a crystalline Form XIX ofAP1189 oxoglutarate exhibiting one or more X-ray lines (2-theta values)in a powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 9.1, 10.7, 11.8, 12.0, 12.8, 13.2,13.4, 13.8, 14.0, 15.9, 16.4, 16.8, 17.1, 17.9, 18.3, 19.5, 20.1, 20.8,21.6, 22.0, 22.9, 23.4, 23.6, 24.1, 24.2, 25.8, 26.5, 26.9, 27.4, 27.9,28.9, 29.9, 30.3, 30.9, 32.3, 32.6, 33.1, 33.8, and 34.7. One embodimentof the disclosure provides for a crystalline Form XIX of AP1189oxoglutarate exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 9.1±0.2, 10.7±0.2, 11.8±0.2,12.0±0.2, 12.8±0.2, 13.2±0.2, 13.4±0.2, 13.8±0.2, 14.0±0.2, 15.9±0.2,16.4±0.2, 16.8±0.2, 17.1±0.2, 17.9±0.2, 18.3±0.2, 19.5±0.2, 20.1±0.2,20.8±0.2, 21.6±0.2, 22.0±0.2, 22.9±0.2, 23.4±0.2, 23.6±0.2, 24.1±0.2,24.2±0.2, 25.8±0.2, 26.5±0.2, 26.9±0.2, 27.4±0.2, 27.9±0.2, 28.9±0.2,29.9±0.2, 30.3±0.2, 30.9±0.2, 32.3±0.2, 32.6±0.2, 33.1±0.2, 33.8±0.2,and 34.7±0.2. It may be advantageous to identify the crystalline FormXIX of AP1189 oxoglutarate by X-ray lines (2-theta values) having a highrelative intensity, and/or by characteristic X-ray lines. Thus, oneembodiment of the present disclosure provides for a crystalline Form XIXof AP1189 oxoglutarate exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 9.1, 10.7, 12.8, 13.2,13.4, 16.4, 16.8, 20.8, 21.6, 23.4, 23.6, 24.1, 24.2, 26.5, and 26.9.One embodiment of the present disclosure provides for a crystalline FormXIX of AP1189 oxoglutarate exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 9.1±0.2, 10.7±0.2,12.8±0.2, 13.2±0.2, 13.4±0.2, 16.4±0.2, 16.8±0.2, 20.8±0.2, 21.6±0.2,23.4±0.2, 23.6±0.2, 24.1±0.2, 24.2±0.2, 26.5±0.2, and 26.9±0.2. Oneembodiment of the present disclosure provides for a crystalline Form XIXof AP1189 oxoglutarate exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of the 2-theta values inlisted in Table 25.

AP1189 DL-Mandelic Acid Form XX

The present disclosure provides for a crystalline Form XX of AP1189DL-mandelic acid. Crystalline Form XX of AP1189 DL-mandelic acidexhibits an XRPD diffractogram as shown in FIG. 31 . One embodiment ofthe present disclosure provides for a crystalline Form XX of AP1189DL-mandelic acid exhibiting at least X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiation at14.8±0.2, 24.2±0.2, and 25.5±0.2. One embodiment provides for acrystalline Form XX of AP1189 DL-mandelic acid further exhibiting one ormore X-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of9.6±0.2, 10.0±0.2, 19.1±0.2, and 21.5±0.2. One embodiment of the presentdisclosure provides for a crystalline Form XX of AP1189 DL-mandelic acidfurther exhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 5.3±0.2, 12.4±0.2, 13.3±0.2, 16.0±0.2, 16.8±0.2,17.9±0.2, 21.2±0.2, and 24.8±0.2. One embodiment of the disclosureprovides for a crystalline Form XX of AP1189 DL-mandelic acid exhibitingan X-ray pattern (2-theta values) in a powder diffraction when measuredusing Cu K_(α) radiation according to FIG. 31 .

One embodiment of the disclosure provides for a crystalline Form XX ofAP1189 DL-mandelic acid exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 5.3, 9.6, 10.0, 10.7,10.9, 11.7, 12.0, 12.4, 13.3, 13.9, 14.8, 15.3, 16.0, 16.8, 17.0, 17.3,17.6, 17.9, 18.5, 19.1, 19.8, 20.2, 20.7, 21.2, 21.5, 21.8, 22.9, 24.2,24.5, 24.8, 25.5, 26.4, 26.9, 27.1, 27.5, 28.1, 28.4, 29.7, 30.3, 31.2,32.4, 32.8, 33.1, 33.5, 34.4, and 34.7. One embodiment of the disclosureprovides for a crystalline Form XX of AP1189 DL-mandelic acid exhibitingone or more X-ray lines (2-theta values) in a powder diffraction patternwhen measured using Cu K_(α) radiation selected from the groupconsisting of 5.3±0.2, 9.6±0.2, 10.0±0.2, 10.7±0.2, 10.9±0.2, 11.7±0.2,12.0±0.2, 12.4±0.2, 13.3±0.2, 13.9±0.2, 14.8±0.2, 15.3±0.2, 16.0±0.2,16.8±0.2, 17.0±0.2, 17.3±0.2, 17.6±0.2, 17.9±0.2, 18.5±0.2, 19.1±0.2,19.8±0.2, 20.2±0.2, 20.7±0.2, 21.2±0.2, 21.5±0.2, 21.8±0.2, 22.9±0.2,24.2±0.2, 24.5±0.2, 24.8±0.2, 25.5±0.2, 26.4±0.2, 26.9±0.2, 27.1±0.2,27.5±0.2, 28.1±0.2, 28.4±0.2, 29.7±0.2, 30.3±0.2, 31.2±0.2, 32.4±0.2,32.8±0.2, 33.1±0.2, 33.5±0.2, 34.4±0.2, and 34.7±0.2. It may beadvantageous to identify the crystalline Form XX of AP1189 DL-mandelicacid by X-ray lines (2-theta values) having a high relative intensity,and/or by characteristic X-ray lines. Thus, one embodiment of thepresent disclosure provides for a crystalline Form XX of AP1189DL-mandelic acid exhibiting one or more X-ray lines (2-theta values) ina powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 5.3, 9.6, 10.0, 12.4, 13.3, 14.8,16.0, 16.8, 17.9, 19.1, 21.2, 21.5, 24.2, 24.8, and 25.5. One embodimentof the present disclosure provides for a crystalline Form XX of AP1189DL-mandelic acid exhibiting one or more X-ray lines (2-theta values) ina powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 5.3±0.2, 9.6±0.2, 10.0±0.2,12.4±0.2, 13.3±0.2, 14.8±0.2, 16.0±0.2, 16.8±0.2, 17.9±0.2, 19.1±0.2,21.2±0.2, 21.5±0.2, 24.2±0.2, 24.8±0.2, and 25.5±0.2. One embodiment ofthe present disclosure provides for a crystalline Form XX of AP1189DL-mandelic acid exhibiting one or more X-ray lines (2-theta values) ina powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of the 2-theta values in listed inTable 26.

AP1189 DL-Mandelic Acid Form XXI

The present disclosure provides for a crystalline Form XXI of AP1189DL-mandelic acid. Crystalline Form XXI of AP1189 DL-mandelic acidexhibits an XRPD diffractogram as shown in FIG. 32 . One embodiment ofthe present disclosure provides for a crystalline Form XXI of AP1189DL-mandelic acid exhibiting at least X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiation at5.4±0.2, 10.0±0.2, and 24.6±0.2. One embodiment provides for acrystalline Form XXI of AP1189 further exhibiting one or more X-raylines (2-theta values) in a powder diffraction pattern when measuredusing Cu K_(α) radiation selected from the group consisting of 9.8±0.2,16.6±0.2, 18.1±0.2, and 21.1±0.2. One embodiment of the presentdisclosure provides for a crystalline Form XXI of AP1189 DL-mandelicacid further exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 12.7±0.2, 13.5±0.2, 21.7±0.2, and25.4±0.2. One embodiment of the disclosure provides for a crystallineForm XXI of AP1189 DL-mandelic acid exhibiting an X-ray pattern (2-thetavalues) in a powder diffraction when measured using Cu K_(α) radiationaccording to FIG. 32 .

One embodiment of the disclosure provides for a crystalline Form XXI ofAP1189 DL-mandelic acid exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 5.4, 9.8, 10.0, 11.2,11.5, 11.8, 12.7, 13.5, 14.4, 15.0, 15.5, 15.7, 15.8, 16.6, 17.2, 18.1,19.6, 20.2, 20.7, 21.1, 21.7, 22.6, 23.3, 23.6, 24.6, 25.4, 26.1, 27.0,27.3, 28.7, 29.0, 29.8, 30.4, 30.7, 31.2, 32.8, 33.5, 34.0, and 34.5.One embodiment of the disclosure provides for a crystalline Form XXI ofAP1189 DL-mandelic acid exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 5.4±0.2, 9.8±0.2,10.0±0.2, 11.2±0.2, 11.5±0.2, 11.8±0.2, 12.7±0.2, 13.5±0.2, 14.4±0.2,15.0±0.2, 15.5±0.2, 15.7±0.2, 15.8±0.2, 16.6±0.2, 17.2±0.2, 18.1±0.2,19.6±0.2, 20.2±0.2, 20.7±0.2, 21.1±0.2, 21.7±0.2, 22.6±0.2, 23.3±0.2,23.6±0.2, 24.6±0.2, 25.4±0.2, 26.1±0.2, 27.0±0.2, 27.3±0.2, 28.7±0.2,29.0±0.2, 29.8±0.2, 30.4±0.2, 30.7±0.2, 31.2±0.2, 32.8±0.2, 33.5±0.2,34.0±0.2, and 34.5±0.2. It may be advantageous to identify thecrystalline Form XXI of AP1189 DL-mandelic acid by X-ray lines (2-thetavalues) having a high relative intensity, and/or by characteristic X-raylines. Thus, one embodiment of the present disclosure provides for acrystalline Form XXI of AP1189 DL-mandelic acid exhibiting one or moreX-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of5.4, 9.8, 10.0, 12.7, 13.5, 16.6, 18.1, 21.1, 21.7, 24.6, and 25.4. Oneembodiment of the present disclosure provides for a crystalline Form XXIof AP1189 DL-mandelic acid exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 5.4±0.2, 9.8±0.2,10.0±0.2, 12.7±0.2, 13.5±0.2, 16.6±0.2, 18.1±0.2, 21.1±0.2, 21.7±0.2,24.6±0.2, and 25.4±0.2. One embodiment of the present disclosureprovides for a crystalline Form XXI of AP1189 DL-mandelic acidexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of the 2-theta values in listed in Table 27.

AP1189 Hippuric Acid Form XXII

The present disclosure provides for a crystalline Form XXII of AP1189hippuric acid. Crystalline Form XXII of AP1189 hippuric acid exhibits anXRPD diffractogram as shown in FIG. 33 . One embodiment of the presentdisclosure provides for a crystalline Form XXII of AP1189 hippuricexhibiting at least X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation at 20.1±0.2, 24.1±0.2,and 24.5±0.2. One embodiment provides for a crystalline Form XXII ofAP1189 hippuric acid further exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 10.9±0.2, 11.5±0.2,14.4±0.2, 14.9±0.2, and 18.1±0.2. One embodiment of the presentdisclosure provides for a crystalline Form XXII of AP1189 hippuric acidfurther exhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 9.6±0.2, 14.1±0.2, and 15.5±0.2. One embodimentof the disclosure provides for a crystalline Form XXII of AP1189hippuric acid exhibiting an X-ray pattern (2-theta values) in a powderdiffraction when measured using Cu K_(α) radiation according to FIG. 33.

One embodiment of the disclosure provides for a crystalline Form XXII ofAP1189 hippuric acid exhibiting one or more X-ray lines (2-theta values)in a powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 8.6, 9.6, 9.8, 10.9, 11.5, 11.8,12.7, 13.3, 13.8, 14.1, 14.4, 14.9, 15.5, 16.4, 17.5, 18.1, 19.5, 20.1,20.7, 21.0, 22.0, 22.4, 22.8, 23.1, 24.1, 24.5, 25.3, 25.8, 27.1, 28.1,and 29.1. One embodiment of the disclosure provides for a crystallineForm XXII of AP1189 hippuric acid exhibiting one or more X-ray lines(2-theta values) in a powder diffraction pattern when measured using CuK_(α) radiation selected from the group consisting of 8.6±0.2, 9.6±0.2,9.8±0.2, 10.9±0.2, 11.5±0.2, 11.8±0.2, 12.7±0.2, 13.3±0.2, 13.8±0.2,14.1±0.2, 14.4±0.2, 14.9±0.2, 15.5±0.2, 16.4±0.2, 17.5±0.2, 18.1±0.2,19.5±0.2, 20.1±0.2, 20.7±0.2, 21.0±0.2, 22.0±0.2, 22.4±0.2, 22.8±0.2,23.1±0.2, 24.1±0.2, 24.5±0.2, 25.3±0.2, 25.8±0.2, 27.1±0.2, 28.1±0.2,and 29.1±0.2. It may be advantageous to identify the crystalline FormXXII of AP1189 hippuric acid by X-ray lines (2-theta values) having ahigh relative intensity, and/or by characteristic X-ray lines. Thus, oneembodiment of the present disclosure provides for a crystalline FormXXII of AP1189 hippuric acid exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 9.6, 10.9, 11.5, 14.1,14.4, 14.9, 15.5, 18.1, 20.1, 24.1, and 24.5. One embodiment of thepresent disclosure provides for a crystalline Form XXII of AP1189hippuric acid exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 9.6±0.2, 10.9±0.2, 11.5±0.2,14.1±0.2, 14.4±0.2, 14.9±0.2, 15.5±0.2, 18.1±0.2, 20.1±0.2, 24.1±0.2,and 24.5±0.2. One embodiment of the present disclosure provides for acrystalline Form XXII of AP1189 hippuric acid exhibiting one or moreX-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting ofthe 2-theta values in listed in Table 28.

AP1189 Formic Acid Form XXIII

The present disclosure provides for a crystalline Form XXIII of AP1189formate. Crystalline Form XXIII of AP1189 formate exhibits an XRPDdiffractogram as shown in FIG. 34 . One embodiment of the presentdisclosure provides for a crystalline Form XXIII of AP1189 formateexhibiting at least X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation at 13.3±0.2, 15.1±0.2,and 25.6±0.2. One embodiment provides for a crystalline Form XXIII ofAP1189 formate further exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 17.3±0.2, 18.9±0.2,21.8±0.2, and 23.6±0.2. One embodiment of the present disclosureprovides for a crystalline Form XXIII of AP1189 formate furtherexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 12.2±0.2, 20.6±0.2, 22.8±0.2, 28.9±0.2, and29.2±0.2. One embodiment of the disclosure provides for a crystallineForm XXIII of AP1189 formate exhibiting an X-ray pattern (2-thetavalues) in a powder diffraction when measured using Cu K_(α) radiationaccording to FIG. 34 .

One embodiment of the disclosure provides for a crystalline Form XXIIIof AP1189 formate exhibiting one or more X-ray lines (2-theta values) ina powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 7.4, 10.4, 10.6, 12.2, 13.3, 14.1,15.1, 15.2, 16.8, 17.3, 18.0, 18.5, 18.8, 18.9, 19.1, 20.6, 20.9, 21.4,21.8, 22.3, 22.6, 22.8, 23.1, 23.6, 24.0, 24.5, 24.9, 25.6, 26.8, 27.1,27.6, 28.1, 28.6, 28.9, 29.2, 30.5, 30.9, 31.7, 32.2, 32.7, 33.1, and34.0. One embodiment of the disclosure provides for a crystalline FormXXIII of AP1189 formate exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 7.4±0.2, 10.4±0.2,10.6±0.2, 12.2±0.2, 13.3±0.2, 14.1±0.2, 15.1±0.2, 15.2±0.2, 16.8±0.2,17.3±0.2, 18.0±0.2, 18.5±0.2, 18.8±0.2, 18.9±0.2, 19.1±0.2, 20.6±0.2,20.9±0.2, 21.4±0.2, 21.8±0.2, 22.3±0.2, 22.6±0.2, 22.8±0.2, 23.1±0.2,23.6±0.2, 24.0±0.2, 24.5±0.2, 24.9±0.2, 25.6±0.2, 26.8±0.2, 27.1±0.2,27.6±0.2, 28.1±0.2, 28.6±0.2, 28.9±0.2, 29.2±0.2, 30.5±0.2, 30.9±0.2,31.7±0.2, 32.2±0.2, 32.7±0.2, 33.1±0.2, and 34.0±0.2. It may beadvantageous to identify the crystalline Form XXIII of AP1189 formate byX-ray lines (2-theta values) having a high relative intensity, and/or bycharacteristic X-ray lines. Thus, one embodiment of the presentdisclosure provides for a crystalline Form XXIII of AP1189 formateexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 12.2, 13.3, 15.1, 17.3, 18.9, 20.6, 21.8, 22.8,23.6, 25.6, 28.9, and 29.2. One embodiment of the present disclosureprovides for a crystalline Form XXIII of AP1189 formate exhibiting oneor more X-ray lines (2-theta values) in a powder diffraction patternwhen measured using Cu K_(α) radiation selected from the groupconsisting of 12.2±0.2, 13.3±0.2, 15.1±0.2, 17.3±0.2, 18.9±0.2,20.6±0.2, 21.8±0.2, 22.8±0.2, 23.6±0.2, 25.6±0.2, 28.9±0.2, and29.2±0.2. One embodiment of the present disclosure provides for acrystalline Form XXIII of AP1189 formate exhibiting one or more X-raylines (2-theta values) in a powder diffraction pattern when measuredusing Cu K_(α) radiation selected from the group consisting of the2-theta values in listed in Table 29.

AP1189 DL-Lactic Acid Form XXIV

The present disclosure provides for a crystalline Form XXIV of AP1189DL-lactic acid. Crystalline Form XXIV of AP1189 DL-lactic acid exhibitsan XRPD diffractogram as shown in FIG. 35 . One embodiment of thepresent disclosure provides for a crystalline Form XXIV of AP1189DL-lactic acid exhibiting at least X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiation at3.8±0.2, 9.9±0.2, and 11.9±0.2. One embodiment provides for acrystalline Form XXIV of AP1189 DL-lactic acid further exhibiting one ormore X-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of7.7±0.2, 23.0±0.2, and 27.5±0.2. One embodiment of the presentdisclosure provides for a crystalline Form XXIV of AP1189 DL-lactic acidfurther exhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 15.4±0.2, 23.9±0.2, and 25.3±0.2. One embodimentof the disclosure provides for a crystalline Form XXIV of AP1189DL-lactic acid exhibiting an X-ray pattern (2-theta values) in a powderdiffraction when measured using Cu K_(α) radiation according to FIG. 35.

One embodiment of the disclosure provides for a crystalline Form XXIV ofAP1189 DL-lactic exhibiting one or more X-ray lines (2-theta values) ina powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 3.8, 7.7, 9.9, 11.9, 13.6, 14.0,14.2, 14.7, 15.4, 15.8, 18.0, 18.3, 18.7, 19.3, 19.8, 20.2, 20.4, 20.7,20.9, 21.4, 21.6, 22.4, 22.6, 23.0, 23.3, 23.7, 23.9, 25.3, 25.9, 27.5,27.8, 28.5, 28.7, 29.6, 30.0, 30.4, 31.4, 31.8, 33.1, and 33.6. Oneembodiment of the disclosure provides for a crystalline Form XXIV ofAP1189 DL-lactic acid exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 3.8±0.2, 7.7±0.2,9.9±0.2, 11.9±0.2, 13.6±0.2, 14.0±0.2, 14.2±0.2, 14.7±0.2, 15.4±0.2,15.8±0.2, 18.0±0.2, 18.3±0.2, 18.7±0.2, 19.3±0.2, 19.8±0.2, 20.2±0.2,20.4±0.2, 20.7±0.2, 20.9±0.2, 21.4±0.2, 21.6±0.2, 22.4±0.2, 22.6±0.2,23.0±0.2, 23.3±0.2, 23.7±0.2, 23.9±0.2, 25.3±0.2, 25.9±0.2, 27.5±0.2,27.8±0.2, 28.5±0.2, 28.7±0.2, 29.6±0.2, 30.0±0.2, 30.4±0.2, 31.4±0.2,31.8±0.2, 33.1±0.2, and 33.6±0.2. It may be advantageous to identify thecrystalline Form XXIV of AP1189 DL-lactic acid by X-ray lines (2-thetavalues) having a high relative intensity, and/or by characteristic X-raylines. Thus, one embodiment of the present disclosure provides for acrystalline Form XXIV of AP1189 DL-lactic acid exhibiting one or moreX-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of3.8, 7.7, 9.9, 11.9, 15.4, 23.0, 23.9, 25.3, and 27.5. One embodiment ofthe present disclosure provides for a crystalline Form XXIV of AP1189DL-lactic acid exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 3.8±0.2, 7.7±0.2, 9.9±0.2,11.9±0.2, 15.4±0.2, 23.0±0.2, 23.9±0.2, 25.3±0.2, and 27.5±0.2. Oneembodiment of the present disclosure provides for a crystalline FormXXIV of AP1189 DL-lactic acid exhibiting one or more X-ray lines(2-theta values) in a powder diffraction pattern when measured using CuK_(α) radiation selected from the group consisting of the 2-theta valuesin listed in Table 30.

AP1189 DL-Lactic Acid Form XXV

The present disclosure provides for a crystalline Form XXV of AP1189DL-lactic acid. Crystalline Form XXV of AP1189 DL-lactic acid exhibitsan XRPD diffractogram as shown in FIG. 36 . One embodiment of thepresent disclosure provides for a crystalline Form XXV of AP1189DL-lactic acid exhibiting at least X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiation at9.8±0.2, 11.9±0.2, and 27.6±0.2. One embodiment provides for acrystalline Form XXV of AP1189 DL-lactic acid further exhibiting one ormore X-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of3.8±0.2, 23.3±0.2, and 23.9±0.2. One embodiment of the presentdisclosure provides for a crystalline Form XXV of AP1189 DL-lactic acidfurther exhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 7.6±0.2, 15.3±0.2, and 25.6±0.2. One embodimentof the disclosure provides for a crystalline Form XXV of AP1189DL-lactic acid exhibiting an X-ray pattern (2-theta values) in a powderdiffraction when measured using Cu K_(α) radiation according to FIG. 36.

One embodiment of the disclosure provides for a crystalline Form XXV ofAP1189 DL-lactic acid exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 3.8, 7.6, 9.8, 11.9,13.7, 14.1, 14.3, 15.3, 15.8, 18.2, 18.6, 19.2, 19.8, 20.5, 21.0, 21.3,21.5, 22.5, 22.7, 22.9, 23.3, 23.6, 23.9, 25.0, 25.6, 26.1, 27.6, 28.7,29.4, 29.6, 29.8, 30.2, 30.6, 31.6, 32.0, and 34.1. One embodiment ofthe disclosure provides for a crystalline Form XXV of AP1189 DL-lacticacid exhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 3.8±0.2, 7.6±0.2, 9.8±0.2, 11.9±0.2, 13.7±0.2,14.1±0.2, 14.3±0.2, 15.3±0.2, 15.8±0.2, 18.2±0.2, 18.6±0.2, 19.2±0.2,19.8±0.2, 20.5±0.2, 21.0±0.2, 21.3±0.2, 21.5±0.2, 22.5±0.2, 22.7±0.2,22.9±0.2, 23.3±0.2, 23.6±0.2, 23.9±0.2, 25.0±0.2, 25.6±0.2, 26.1±0.2,27.6±0.2, 28.7±0.2, 29.4±0.2, 29.6±0.2, 29.8±0.2, 30.2±0.2, 30.6±0.2,31.6±0.2, 32.0±0.2, and 34.1±0.2. It may be advantageous to identify thecrystalline Form XXV of AP1189 DL-lactic acid by X-ray lines (2-thetavalues) having a high relative intensity, and/or by characteristic X-raylines. Thus, one embodiment of the present disclosure provides for acrystalline Form XXV of AP1189 DL-lactic acid exhibiting one or moreX-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of3.8, 7.6, 9.8, 11.9, 15.3, 23.3, 23.9, 25.6, and 27.6. One embodiment ofthe present disclosure provides for a crystalline Form XXV of AP1189DL-lactic acid exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 3.8±0.2, 7.6±0.2, 9.8±0.2,11.9±0.2, 15.3±0.2, 23.3±0.2, 23.9±0.2, 25.6±0.2, and 27.6±0.2. Oneembodiment of the present disclosure provides for a crystalline Form XXVof AP1189 DL-lactic acid exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of the 2-theta values inlisted in Table 31.

AP1189 Glutaric Acid Form XXVI

The present disclosure provides for a crystalline Form XXVI of AP1189glutaric acid. Crystalline Form XXVI of AP1189 glutaric acid exhibits anXRPD diffractogram as shown in FIG. 37 . One embodiment of the presentdisclosure provides for a crystalline Form XXVI of AP1189 glutaric acidexhibiting at least X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation at 8.3±0.2, 15.9±0.2, and21.9±0.2. One embodiment provides for a crystalline Form XXVI of AP1189glutaric acid further exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 12.8±0.2, 15.1±0.2, and27.1±0.2. One embodiment of the present disclosure provides for acrystalline Form XXVI of AP1189 glutaric acid further exhibiting one ormore X-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of3.2±0.2, 8.7±0.2, 14.4±0.2, 16.2±0.2, 19.0±0.2, 19.8±0.2, 28.8±0.2, and29.5±0.2. One embodiment of the disclosure provides for a crystallineForm XXVI of AP1189 glutaric acid exhibiting an X-ray pattern (2-thetavalues) in a powder diffraction when measured using Cu K_(α) radiationaccording to FIG. 37 .

One embodiment of the disclosure provides for a crystalline Form XXVI ofAP1189 glutaric acid exhibiting one or more X-ray lines (2-theta values)in a powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 3.2, 6.3, 8.3, 8.7, 9.8, 10.1,10.5, 12.8, 13.6, 14.4, 15.1, 15.9, 16.2, 17.1, 17.5, 18.0, 18.3, 19.0,19.8, 20.2, 20.5, 21.0, 21.4, 21.7, 21.9, 23.0, 23.6, 24.1, 24.5, 25.0,26.0, 26.5, 27.1, 27.6, 28.2, 28.8, 29.5, 30.6, 31.4, 32.3, and 33.8.One embodiment of the disclosure provides for a crystalline Form XXVI ofAP1189 glutaric acid exhibiting one or more X-ray lines (2-theta values)in a powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 3.2±0.2, 6.3±0.2, 8.3±0.2,8.7±0.2, 9.8±0.2, 10.1±0.2, 10.5±0.2, 12.8±0.2, 13.6±0.2, 14.4±0.2,15.1±0.2, 15.9±0.2, 16.2±0.2, 17.1±0.2, 17.5±0.2, 18.0±0.2, 18.3±0.2,19.0±0.2, 19.8±0.2, 20.2±0.2, 20.5±0.2, 21.0±0.2, 21.4±0.2, 21.7±0.2,21.9±0.2, 23.0±0.2, 23.6±0.2, 24.1±0.2, 24.5±0.2, 25.0±0.2, 26.0±0.2,26.5±0.2, 27.1±0.2, 27.6±0.2, 28.2±0.2, 28.8±0.2, 29.5±0.2, 30.6±0.2,31.4±0.2, 32.3±0.2, and 33.8±0.2. It may be advantageous to identify thecrystalline Form XXVI of AP1189 glutaric acid by X-ray lines (2-thetavalues) having a high relative intensity, and/or by characteristic X-raylines. Thus, one embodiment of the present disclosure provides for acrystalline Form XXVI of AP1189 glutaric acid exhibiting one or moreX-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of3.2, 8.3, 8.7, 12.8, 14.4, 15.1, 15.9, 16.2, 19.0, 19.8, 21.9, 27.1,28.8, and 29.5. One embodiment of the present disclosure provides for acrystalline Form XXVI of AP1189 glutaric acid exhibiting one or moreX-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of3.2±0.2, 8.3±0.2, 8.7±0.2, 12.8±0.2, 14.4±0.2, 15.1±0.2, 15.9±0.2,16.2±0.2, 19.0±0.2, 19.8±0.2, 21.9±0.2, 27.1±0.2, 28.8±0.2, and29.5±0.2. One embodiment of the present disclosure provides for acrystalline Form XXVI of AP1189 glutaric acid exhibiting one or moreX-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting ofthe 2-theta values in listed in Table 32.

AP1189 Glutaric Acid Form XXVII

The present disclosure provides for a crystalline Form XXVII of AP1189glutaric acid. Crystalline Form XXVII of AP1189 glutaric acid exhibitsan XRPD diffractogram as shown in FIG. 38 . One embodiment of thepresent disclosure provides for a crystalline Form XXVII of AP1189glutaric acid exhibiting at least X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiation at14.1±0.2, 21.7±0.2, and 25.0±0.2. One embodiment provides for acrystalline Form XXVII of AP1189 glutaric acid further exhibiting one ormore X-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting of16.9±0.2, 25.6±0.2, 27.1±0.2, 28.2±0.2, and 28.7±0.2. One embodiment ofthe present disclosure provides for a crystalline Form XXVII of AP1189glutaric acid further exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 6.3±0.2, 10.1±0.2,14.3±0.2, 14.7±0.2, 15.1±0.2, 17.4±0.2, 21.1±0.2, 22.6±0.2, and26.5±0.2. One embodiment of the disclosure provides for a crystallineForm XXVII of AP1189 glutaric acid exhibiting an X-ray pattern (2-thetavalues) in a powder diffraction when measured using Cu K_(α) radiationaccording to FIG. 38 .

One embodiment of the disclosure provides for a crystalline Form XXVIIof AP1189 glutaric acid exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 6.3, 10.1, 10.8, 12.6,12.7, 13.5, 14.1, 14.3, 14.7, 15.1, 15.3, 15.7, 16.5, 16.7, 16.9, 17.4,18.0, 18.3, 18.7, 18.9, 19.3, 19.6, 20.1, 20.2, 20.5, 20.9, 21.3, 21.7,22.1, 22.6, 23.2, 24.0, 24.4, 25.0, 25.6, 26.0, 26.5, 26.8, 27.1, 27.6,28.2, 28.7, 29.0, 29.4, 29.7, 30.5, 31.3, 32.0, 33.0, and 34.1. Oneembodiment of the disclosure provides for a crystalline Form XXVII ofAP1189 glutaric acid exhibiting one or more X-ray lines (2-theta values)in a powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 6.3±0.2, 10.1±0.2, 10.8±0.2,12.6±0.2, 12.7±0.2, 13.5±0.2, 14.1±0.2, 14.3±0.2, 14.7±0.2, 15.1±0.2,15.3±0.2, 15.7±0.2, 16.5±0.2, 16.7±0.2, 16.9±0.2, 17.4±0.2, 18.0±0.2,18.3±0.2, 18.7±0.2, 18.9±0.2, 19.3±0.2, 19.6±0.2, 20.1±0.2, 20.2±0.2,20.5±0.2, 20.9±0.2, 21.3±0.2, 21.7±0.2, 22.1±0.2, 22.6±0.2, 23.2±0.2,24.0±0.2, 24.4±0.2, 25.0±0.2, 25.6±0.2, 26.0±0.2, 26.5±0.2, 26.8±0.2,27.1±0.2, 27.6±0.2, 28.2±0.2, 28.7±0.2, 29.0±0.2, 29.4±0.2, 29.7±0.2,30.5±0.2, 31.3±0.2, 32.0±0.2, 33.0±0.2, and 34.1±0.2. It may beadvantageous to identify the crystalline Form XXVII of AP1189 glutaricacid by X-ray lines (2-theta values) having a high relative intensity,and/or by characteristic X-ray lines. Thus, one embodiment of thepresent disclosure provides for a crystalline Form XXVII of AP1189glutaric acid exhibiting one or more X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 6.3, 10.1, 14.1, 14.3, 14.7, 15.1,16.9, 17.4, 21.7, 22.1, 22.6, 25.0, 25.6, 26.5, 27.1, 28.2, and 28.7.One embodiment of the present disclosure provides for a crystalline FormXXVII of AP1189 glutaric acid exhibiting one or more X-ray lines(2-theta values) in a powder diffraction pattern when measured using CuK_(α) radiation selected from the group consisting of 6.3±0.2, 10.1±0.2,14.1±0.2, 14.3±0.2, 14.7±0.2, 15.1±0.2, 16.9±0.2, 17.4±0.2, 21.7±0.2,22.1±0.2, 22.6±0.2, 25.0±0.2, 25.6±0.2, 26.5±0.2, 27.1±0.2, 28.2±0.2,and 28.7±0.2. One embodiment of the present disclosure provides for acrystalline Form XXVII of AP1189 glutaric acid exhibiting one or moreX-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting ofthe 2-theta values in listed in Table 33.

AP1189 Glutaric Acid Form XXVIII

The present disclosure provides for a crystalline Form XXVIII of AP1189glutaric acid. Crystalline Form XXVIII of AP1189 glutaric acid exhibitsan XRPD diffractogram as shown in FIG. 91 . One embodiment of thepresent disclosure provides for a crystalline Form XXVIII of AP1189glutaric acid exhibiting at least X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiation at14.2±0.2, 16.9±0.2, and 24.5±0.2. One embodiment provides for acrystalline Form XXVIII of AP1189 glutaric acid further exhibiting oneor more X-ray lines (2-theta values) in a powder diffraction patternwhen measured using Cu K_(α) radiation selected from the groupconsisting of 6.3±0.2, 15.2±0.2, 20.9±0.2, and 21.9±0.2. One embodimentof the present disclosure provides for a crystalline Form XXVIII ofAP1189 glutaric acid further exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 8.9±0.2, 10.1±0.2,12.6±0.2, 17.4±0.2, 19.1±0.2, 20.6±0.2, and 28.4±0.2. One embodiment ofthe disclosure provides for a crystalline Form XXVIII of AP1189 glutaricacid exhibiting an X-ray pattern (2-theta values) in a powderdiffraction when measured using Cu K_(α) radiation according to FIG. 91.

One embodiment of the disclosure provides for a crystalline Form XXVIIIof AP1189 glutaric acid exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 6.3, 8.9, 10.1, 10.4,10.7, 12.6, 13.4, 13.8, 14.2, 15.2, 15.6, 16.5, 16.9, 17.4, 18.2, 19.1,19.8, 20.2, 20.6, 20.9, 21.7, 21.9, 22.5, 23.0, 23.6, 23.8, 24.5, 24.9,25.3, 26.1, 27.2, 27.8, 28.4, 29.3, 29.6, 30.5, 31.0, 31.4, 32.4, 33.6,and 34.3. One embodiment of the disclosure provides for a crystallineForm XXVIII of AP1189 glutaric acid exhibiting one or more X-ray lines(2-theta values) in a powder diffraction pattern when measured using CuK_(α) radiation selected from the group consisting of 6.3±0.2, 8.9±0.2,10.1±0.2, 10.4±0.2, 10.7±0.2, 12.6±0.2, 13.4±0.2, 13.8±0.2, 14.2±0.2,15.2±0.2, 15.6±0.2, 16.5±0.2, 16.9±0.2, 17.4±0.2, 18.2±0.2, 19.1±0.2,19.8±0.2, 20.2±0.2, 20.6±0.2, 20.9±0.2, 21.7±0.2, 21.9±0.2, 22.5±0.2,23.0±0.2, 23.6±0.2, 23.8±0.2, 24.5±0.2, 24.9±0.2, 25.3±0.2, 26.1±0.2,27.2±0.2, 27.8±0.2, 28.4±0.2, 29.3±0.2, 29.6±0.2, 30.5±0.2, 31.0±0.2,31.4±0.2, 32.4±0.2, 33.6±0.2, and 34.3±0.2. It may be advantageous toidentify the crystalline Form XXVIII of AP1189 glutaric acid by X-raylines (2-theta values) having a high relative intensity, and/or bycharacteristic X-ray lines. Thus, one embodiment of the presentdisclosure provides for a crystalline Form XXVIII of AP1189 glutaricacid exhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 6.3, 8.9, 10.1, 12.6, 14.2, 15.2, 16.9, 17.4,19.1, 20.6, 20.9, 21.9, 24.5, and 28.4. One embodiment of the presentdisclosure provides for a crystalline Form XXVIII of AP1189 glutaricacid exhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 6.3±0.2, 8.9±0.2, 10.1±0.2, 12.6±0.2, 14.2±0.2,15.2±0.2, 16.9±0.2, 17.4±0.2, 19.1±0.2, 20.6±0.2, 20.9±0.2, 21.9±0.2,24.5±0.2, and 28.4±0.2. One embodiment of the present disclosureprovides for a crystalline Form XXVIII of AP1189 glutaric acidexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of the 2-theta values in listed in Table 34.

AP1189 Adipic Acid Form XXIX

The present disclosure provides for a crystalline Form XXIX of AP1189adipic acid. Crystalline Form XXIX of AP1189 adipic acid exhibits anXRPD diffractogram as shown in FIG. 39 . One embodiment of the presentdisclosure provides for a crystalline Form XXIX of AP1189 adipic acidexhibiting at least X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation at 13.4±0.2, 14.5±0.2,and 25.5±0.2. One embodiment provides for a crystalline Form XXIX ofAP1189 adipic acid further exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 17.6±0.2, 23.5±0.2,25.4±0.2, and 27.1±0.2. One embodiment of the present disclosureprovides for a crystalline Form XXIX of AP1189 adipic acid furtherexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 5.2±0.2, 19.2±0.2, and 21.4±0.2. One embodimentof the disclosure provides for a crystalline Form XXIX of AP1189 adipicacid exhibiting an X-ray pattern (2-theta values) in a powderdiffraction when measured using Cu K_(α) radiation according to FIG. 39.

One embodiment of the disclosure provides for a crystalline Form XXIX ofAP1189 adipic acid exhibiting one or more X-ray lines (2-theta values)in a powder diffraction pattern when measured using Cu K_(α) radiationselected from the group consisting of 5.2, 10.5, 11.2, 12.7, 13.4, 14.5,15.3, 15.8, 17.1, 17.6, 18.0, 18.8, 19.2, 20.5, 21.0, 21.4, 22.4, 22.8,23.0, 23.5, 23.9, 24.4, 24.8, 25.4, 25.5, 26.1, 26.3, 27.1, 27.5, 28.1,28.9, 29.5, 30.6, 32.2, 33.9, and 34.5. One embodiment of the disclosureprovides for a crystalline Form XXIX of AP1189 adipic acid exhibitingone or more X-ray lines (2-theta values) in a powder diffraction patternwhen measured using Cu K_(α) radiation selected from the groupconsisting of 5.2±0.2, 10.5±0.2, 11.2±0.2, 12.7±0.2, 13.4±0.2, 14.5±0.2,15.3±0.2, 15.8±0.2, 17.1±0.2, 17.6±0.2, 18.0±0.2, 18.8±0.2, 19.2±0.2,20.5±0.2, 21.0±0.2, 21.4±0.2, 22.4±0.2, 22.8±0.2, 23.0±0.2, 23.5±0.2,23.9±0.2, 24.4±0.2, 24.8, 25.4, 25.5, 26.1, 26.3, 27.1, 27.5, 28.1,28.9, 29.5, 30.6, 32.2, 33.9, and 34.5±0.2. It may be advantageous toidentify the crystalline Form XXIX of AP1189 adipic acid by X-ray lines(2-theta values) having a high relative intensity, and/or bycharacteristic X-ray lines. Thus, one embodiment of the presentdisclosure provides for a crystalline Form XXIX of AP1189 adipic acidexhibiting one or more X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation selected fromthe group consisting of 5.2, 13.4, 14.5, 17.6, 19.2, 21.4, 23.5, 25.4,25.5, and 27.1. One embodiment of the present disclosure provides for acrystalline Form XXIX of AP1189 adipic acid exhibiting one or more X-raylines (2-theta values) in a powder diffraction pattern when measuredusing Cu K_(α) radiation selected from the group consisting of 5.2±0.2,13.4±0.2, 14.5±0.2, 17.6±0.2, 19.2±0.2, 21.4±0.2, 23.5±0.2, 25.4±0.2,25.5±0.2, and 27.1±0.2. One embodiment of the present disclosureprovides for a crystalline Form XXIX of AP1189 adipic exhibiting one ormore X-ray lines (2-theta values) in a powder diffraction pattern whenmeasured using Cu K_(α) radiation selected from the group consisting ofthe 2-theta values in listed in Table 35.

Further Characterisation of Crystalline Forms

The salts of AP1189 provided herein may be further characterised by theonset temperatures they exhibit as assessed by differential scanningcalorimetry.

One embodiment of the present disclosure provides for a crystalline FormA of AP1189 acetate exhibiting in differential scanning calorimetry anonset temperature between 185 and 199° C. One specific embodiment of thepresent disclosure provides a crystalline Form A of AP1189 acetateexhibiting in differential scanning calorimetry an onset temperature ofsubstantially 192° C. In a further embodiment, the onset temperature isassessed using a heating rate of 10° C./min. One embodiment of thedisclosure provides for a crystalline Form A of AP1189 acetateexhibiting in differential scanning calorimetry an onset temperature asshown in the examples herein, specifically example 4, and/or in thefigures herein, specifically FIG. 8 . One embodiment of the presentdisclosure provides a crystalline Form A of AP1189 acetate exhibiting adifferential scanning calorimetry thermogram according to FIG. 8 . Oneembodiment of the present disclosure provides for a crystalline Form Aof AP1189 acetate exhibiting in differential scanning calorimetry anonset temperature falling within the interval 192±7° C., such as 192±6°C., such as 192±5° C., such as 192±4° C., such as 192±3° C., such as192±2° C., such as 192±1° C.

One embodiment of the present disclosure provides for a crystalline FormB of AP1189 succinate exhibiting in differential scanning calorimetry anonset temperature between 187 and 201° C. One specific embodiment of thepresent disclosure provides a crystalline Form B of AP1189 succinateexhibiting in differential scanning calorimetry an onset temperature ofsubstantially 194° C. In a further embodiment, the onset temperature isassessed using a heating rate of 10° C./min. One embodiment of thedisclosure provides for a crystalline Form B of AP1189 succinateexhibiting in differential scanning calorimetry an onset temperature asshown in the examples herein, specifically example 4, and/or in thefigures herein, specifically FIG. 13 . One embodiment of the presentdisclosure provides a crystalline Form B of AP1189 succinate exhibitinga differential scanning calorimetry thermogram according to FIG. 13. Oneembodiment of the present disclosure provides for a crystalline Form Bof AP1189 succinate exhibiting in differential scanning calorimetry anonset temperature falling within the interval 195±7° C., such as 195±6°C., such as 195±5° C., such as 1954° C., such as 1953° C., such as195±2° C., such as 195±1° C.

One embodiment of the present disclosure provides for a crystalline FormC of AP1189 tosylate exhibiting in differential scanning calorimetry anonset temperature between 227 and 241° C. One specific embodiment of thepresent disclosure provides a crystalline Form C of AP1189 tosylateexhibiting in differential scanning calorimetry an onset temperature ofsubstantially 234° C. In a further embodiment, the onset temperature isassessed using a heating rate of 10° C./min. One embodiment of thedisclosure provides for a crystalline Form C of AP1189 tosylateexhibiting in differential scanning calorimetry an onset temperature asshown in the examples herein, specifically example 4, and/or in thefigures herein, specifically FIG. 11 . One embodiment of the presentdisclosure provides a crystalline Form C of AP1189 tosylate exhibiting adifferential scanning calorimetry thermogram according to FIG. 11 . Oneembodiment of the present disclosure provides for a crystalline Form Cof AP1189 tosylate exhibiting in differential scanning calorimetry anonset temperature falling within the interval 234±7° C., such as 234±6°C., such as 234±5° C., such as 234±4° C., such as 234±3° C., such as234±2° C., such as 234±1° C.

One embodiment of the present disclosure provides for a crystalline FormD of AP1189 fumarate exhibiting in differential scanning calorimetry anonset temperature between 208 and 222° C. One specific embodiment of thepresent disclosure provides a crystalline Form D of AP1189 fumarateexhibiting in differential scanning calorimetry an onset temperature ofsubstantially 215° C. In a further embodiment, the onset temperature isassessed using a heating rate of 10° C./min. One embodiment of thedisclosure provides for a crystalline Form D of AP1189 fumarateexhibiting in differential scanning calorimetry an onset temperature asshown in the examples herein, specifically example 4, and/or in thefigures herein, specifically FIG. 12 . One embodiment of the presentdisclosure provides a crystalline Form D of AP1189 fumarate exhibiting adifferential scanning calorimetry thermogram according to FIG. 12 . Oneembodiment of the present disclosure provides for a crystalline Form Dof AP1189 fumarate exhibiting in differential scanning calorimetry anonset temperature falling within the interval 215±7° C., such as 215±6°C., such as 215±5° C., such as 215±4° C., such as 215±3° C., such as215±2° C., such as 215±1° C.

Certain salts disclosed herein exhibit more than one onset temperature,e.g. two onset temperatures. The salts may be characterised by either oftheir onset temperatures in isolation, or as a combination of onsettemperatures.

One embodiment of the present disclosure provides for a crystalline FormIII of AP1189 napadisylate exhibiting in differential scanningcalorimetry an onset temperature between 80 and 94° C. One specificembodiment of the present disclosure provides a crystalline Form III ofAP1189 napadisylate exhibiting in differential scanning calorimetry anonset temperature of substantially 87° C. In a further embodiment, theonset temperature is assessed using a heating rate of 10° C./min. Oneembodiment of the disclosure provides for a crystalline Form III ofAP1189 napadisylate exhibiting in differential scanning calorimetry anonset temperature as shown in the examples herein, specifically example4, and/or in the figures herein, specifically FIG. 40 . One embodimentof the present disclosure provides a crystalline Form III of AP1189napadisylate exhibiting a differential scanning calorimetry thermogramaccording to FIG. 40 . One embodiment of the present disclosure providesfor a crystalline Form III of AP1189 napadisylate exhibiting indifferential scanning calorimetry an onset temperature falling withinthe interval 87±7° C., such as 87±6° C., such as 87±5° C., such as 874°C., such as 873° C., such as 87±2° C., such as 87±1° C.

One embodiment of the present disclosure provides for a crystalline FormIII of AP1189 napadisylate exhibiting in differential scanningcalorimetry an onset temperature between 180 and 194° C. One specificembodiment of the present disclosure provides a crystalline Form III ofAP1189 napadisylate exhibiting in differential scanning calorimetry anonset temperature of substantially 187° C. In a further embodiment, theonset temperature is assessed using a heating rate of 10° C./min. Oneembodiment of the disclosure provides for a crystalline Form III ofAP1189 napadisylate exhibiting in differential scanning calorimetry anonset temperature as shown in the examples herein, specifically example4, and/or in the figures herein, specifically FIG. 40 . One embodimentof the present disclosure provides a crystalline Form III of AP1189napadisylate exhibiting a differential scanning calorimetry thermogramaccording to FIG. 40 . One embodiment of the present disclosure providesfor a crystalline Form III of AP1189 napadisylate exhibiting indifferential scanning calorimetry an onset temperature falling withinthe interval 187±7° C., such as 187±6° C., such as 187±5° C., such as187±4° C., such as 187±3° C., such as 187±2° C., such as 187±1° C.

One embodiment of the disclosure provides for a crystalline Form IV ofAP1189 napadisylate exhibiting in differential scanning calorimetry anonset temperature as shown in the examples herein, specifically example4, and/or in the figures herein, specifically FIG. 81 . One embodimentof the present disclosure provides a crystalline Form IV of AP1189napadisylate exhibiting a differential scanning calorimetry thermogramaccording to FIG. 81 .

One embodiment of the present disclosure provides for a crystalline FormV of AP1189 esylate exhibiting in differential scanning calorimetry anonset temperature between 200 and 214° C. One specific embodiment of thepresent disclosure provides a crystalline Form V of AP1189 esylateexhibiting in differential scanning calorimetry an onset temperature ofsubstantially 207° C. In a further embodiment, the onset temperature isassessed using a heating rate of 10° C./min. One embodiment of thedisclosure provides for a crystalline Form V of AP1189 esylateexhibiting in differential scanning calorimetry an onset temperature asshown in the examples herein, specifically example 4, and/or in thefigures herein, specifically FIG. 41 . One embodiment of the presentdisclosure provides a crystalline Form V of AP1189 esylate exhibiting adifferential scanning calorimetry thermogram according to FIG. 41 . Oneembodiment of the present disclosure provides for a crystalline Form Vof AP1189 esylate exhibiting in differential scanning calorimetry anonset temperature falling within the interval 207±7° C., such as 207±6°C., such as 207±5° C., such as 207±4° C., such as 207±3° C., such as207±2° C., such as 207±1° C.

One embodiment of the present disclosure provides for a crystalline FormVI of AP1189 edisylate exhibiting in differential scanning calorimetryan onset temperature between 71 and 85° C. One specific embodiment ofthe present disclosure provides a crystalline Form VI of AP1189edisylate exhibiting in differential scanning calorimetry an onsettemperature of substantially 78° C. In a further embodiment, the onsettemperature is assessed using a heating rate of 10° C./min. Oneembodiment of the disclosure provides for a crystalline Form VI ofAP1189 edisylate exhibiting in differential scanning calorimetry anonset temperature as shown in the examples herein, specifically example4, and/or in the figures herein, specifically FIG. 82 . One embodimentof the present disclosure provides a crystalline Form VI of AP1189edisylate exhibiting a differential scanning calorimetry thermogramaccording to FIG. 82 . One embodiment of the present disclosure providesfor a crystalline Form VI of AP1189 edisylate exhibiting in differentialscanning calorimetry an onset temperature falling within the interval78±7° C., such as 78±6° C., such as 78±5° C., such as 78±4° C., such as78±3° C., such as 78±2° C., such as 78±1° C.

One embodiment of the present disclosure provides for a crystalline FormVI of AP1189 edisylate exhibiting in differential scanning calorimetryan onset temperature between 144 and 158° C. One specific embodiment ofthe present disclosure provides a crystalline Form VI of AP1189edisylate exhibiting in differential scanning calorimetry an onsettemperature of substantially 151° C. In a further embodiment, the onsettemperature is assessed using a heating rate of 10° C./min. Oneembodiment of the disclosure provides for a crystalline Form VI ofAP1189 edisylate exhibiting in differential scanning calorimetry anonset temperature as shown in the examples herein, specifically example4, and/or in the figures herein, specifically FIG. 82 . One embodimentof the present disclosure provides a crystalline Form VI of AP1189edisylate exhibiting a differential scanning calorimetry thermogramaccording to FIG. 82 . One embodiment of the present disclosure providesfor a crystalline Form VI of AP1189 edisylate exhibiting in differentialscanning calorimetry an onset temperature falling within the interval151±7° C., such as 151±6° C., such as 151±5° C., such as 151±4° C., suchas 151±3° C., such as 151±2° C., such as 151±1° C.

One embodiment of the present disclosure provides for a crystalline FormVII of AP1189 edisylate exhibiting in differential scanning calorimetryan onset temperature between 218 and 232° C. One specific embodiment ofthe present disclosure provides a crystalline Form VII of AP1189edisylate exhibiting in differential scanning calorimetry an onsettemperature of substantially 225° C. In a further embodiment, the onsettemperature is assessed using a heating rate of 10° C./min. Oneembodiment of the disclosure provides for a crystalline Form VII ofAP1189 edisylate exhibiting in differential scanning calorimetry anonset temperature as shown in the examples herein, specifically example4, and/or in the figures herein, specifically FIG. 42 . One embodimentof the present disclosure provides a crystalline Form VII of AP1189edisylate exhibiting a differential scanning calorimetry thermogramaccording to FIG. 42. One embodiment of the present disclosure providesfor a crystalline Form VII of AP1189 edisylate exhibiting indifferential scanning calorimetry an onset temperature falling withinthe interval 225±7° C., such as 225±6° C., such as 225±5° C., such as225±4° C., such as 225±3° C., such as 225±2° C., such as 225±1° C.

One embodiment of the present disclosure provides for a crystalline FormVIII of AP1189 edisylate exhibiting in differential scanning calorimetryan onset temperature between 201 and 215° C. One specific embodiment ofthe present disclosure provides a crystalline Form VIII of AP1189edisylate exhibiting in differential scanning calorimetry an onsettemperature of substantially 208° C. In a further embodiment, the onsettemperature is assessed using a heating rate of 10° C./min. Oneembodiment of the disclosure provides for a crystalline Form VIII ofAP1189 edisylate exhibiting in differential scanning calorimetry anonset temperature as shown in the examples herein, specifically example4, and/or in the figures herein, specifically FIG. 43 . One embodimentof the present disclosure provides a crystalline Form VIII of AP1189edisylate exhibiting a differential scanning calorimetry thermogramaccording to FIG. 43 . One embodiment of the present disclosure providesfor a crystalline Form VIII of AP1189 edisylate exhibiting indifferential scanning calorimetry an onset temperature falling withinthe interval 208±7° C., such as 208±6° C., such as 208±5° C., such as208±4° C., such as 208±3° C., such as 208±2° C., such as 208±1° C.

One embodiment of the present disclosure provides for a crystalline FormIX of AP1189 edisylate exhibiting in differential scanning calorimetryan onset temperature between 52 and 66° C. One specific embodiment ofthe present disclosure provides a crystalline Form IX of AP1189edisylate exhibiting in differential scanning calorimetry an onsettemperature of substantially 59° C. In a further embodiment, the onsettemperature is assessed using a heating rate of 10° C./min. Oneembodiment of the disclosure provides for a crystalline Form IX ofAP1189 edisylate exhibiting in differential scanning calorimetry anonset temperature as shown in the examples herein, specifically example4, and/or in the figures herein, specifically FIG. 44 . One embodimentof the present disclosure provides a crystalline Form IX of AP1189edisylate exhibiting a differential scanning calorimetry thermogramaccording to FIG. 44 . One embodiment of the present disclosure providesfor a crystalline Form IX of AP1189 edisylate exhibiting in differentialscanning calorimetry an onset temperature falling within the interval59±7° C., such as 59±6° C., such as 59±5° C., such as 59±4° C., such as59±3° C., such as 59±2° C., such as 59±1° C.

One embodiment of the present disclosure provides for a crystalline FormXI of AP1189 edisylate exhibiting in differential scanning calorimetryan onset temperature between 144 and 158° C. One specific embodiment ofthe present disclosure provides a crystalline Form IX of AP1189edisylate exhibiting in differential scanning calorimetry an onsettemperature of substantially 151° C. In a further embodiment, the onsettemperature is assessed using a heating rate of 10° C./min. Oneembodiment of the disclosure provides for a crystalline Form IX ofAP1189 edisylate exhibiting in differential scanning calorimetry anonset temperature as shown in the examples herein, specifically example4, and/or in the figures herein, specifically FIG. 44 . One embodimentof the present disclosure provides a crystalline Form IX of AP1189edisylate exhibiting a differential scanning calorimetry thermogramaccording to FIG. 44 . One embodiment of the present disclosure providesfor a crystalline Form IX of AP1189 edisylate exhibiting in differentialscanning calorimetry an onset temperature falling within the interval151±7° C., such as 151±6° C., such as 151±5° C., such as 151±4° C., suchas 151±3° C., such as 151±2° C., such as 151±1° C.

One embodiment of the present disclosure provides for a crystalline FormX of AP1189 nitrate exhibiting in differential scanning calorimetry anonset temperature between 172 and 186° C. One specific embodiment of thepresent disclosure provides a crystalline Form X of AP1189 nitrateexhibiting in differential scanning calorimetry an onset temperature ofsubstantially 179° C. In a further embodiment, the onset temperature isassessed using a heating rate of 10° C./min. One embodiment of thedisclosure provides for a crystalline Form X of AP1189 nitrateexhibiting in differential scanning calorimetry an onset temperature asshown in the examples herein, specifically example 4, and/or in thefigures herein, specifically FIG. 45 . One embodiment of the presentdisclosure provides a crystalline Form X of AP1189 nitrate exhibiting adifferential scanning calorimetry thermogram according to FIG. 45 . Oneembodiment of the present disclosure provides for a crystalline Form Xof AP1189 nitrate exhibiting in differential scanning calorimetry anonset temperature falling within the interval 179±7° C., such as 179±6°C., such as 179±5° C., such as 179±4° C., such as 179±3° C., such as179±2° C., such as 179±1° C.

One embodiment of the present disclosure provides for a crystalline FormXI of AP1189 cyclamate exhibiting in differential scanning calorimetryan onset temperature between 123 and 137° C. One specific embodiment ofthe present disclosure provides a crystalline Form XI of AP1189cyclamate exhibiting in differential scanning calorimetry an onsettemperature of substantially 130° C. In a further embodiment, the onsettemperature is assessed using a heating rate of 10° C./min. Oneembodiment of the disclosure provides for a crystalline Form XI ofAP1189 cyclamate exhibiting in differential scanning calorimetry anonset temperature as shown in the examples herein, specifically example4, and/or in the figures herein, specifically FIG. 46 . One embodimentof the present disclosure provides a crystalline Form XI of AP1189cyclamate exhibiting a differential scanning calorimetry thermogramaccording to FIG. 46 . One embodiment of the present disclosure providesfor a crystalline Form XI of AP1189 cyclamate exhibiting in differentialscanning calorimetry an onset temperature falling within the interval130±7° C., such as 130±6° C., such as 130±5° C., such as 130±4° C., suchas 130±3° C., such as 130±2° C., such as 130±1° C.

One embodiment of the present disclosure provides for a crystalline FormXII of AP1189 cyclamate exhibiting in differential scanning calorimetryan onset temperature between 131 and 145° C. One specific embodiment ofthe present disclosure provides a crystalline Form XII of AP1189cyclamate exhibiting in differential scanning calorimetry an onsettemperature of substantially 138° C. In a further embodiment, the onsettemperature is assessed using a heating rate of 10° C./min. Oneembodiment of the disclosure provides for a crystalline Form XII ofAP1189 cyclamate exhibiting in differential scanning calorimetry anonset temperature as shown in the examples herein, specifically example4, and/or in the figures herein, specifically FIG. 47 . One embodimentof the present disclosure provides a crystalline Form XII of AP1189cyclamate exhibiting a differential scanning calorimetry thermogramaccording to FIG. 47 . One embodiment of the present disclosure providesfor a crystalline Form XII of AP1189 cyclamate exhibiting indifferential scanning calorimetry an onset temperature falling withinthe interval 138±7° C., such as 138±6° C., such as 138±5° C., such as138±4° C., such as 138±3° C., such as 138±2° C., such as 138±1° C.

One embodiment of the present disclosure provides for a crystalline FormXIII of AP1189 cyclamate exhibiting in differential scanning calorimetryan onset temperature between 134 and 148° C. One specific embodiment ofthe present disclosure provides a crystalline Form XIII of AP1189cyclamate exhibiting in differential scanning calorimetry an onsettemperature of substantially 141° C. In a further embodiment, the onsettemperature is assessed using a heating rate of 10° C./min. Oneembodiment of the disclosure provides for a crystalline Form XIII ofAP1189 cyclamate exhibiting in differential scanning calorimetry anonset temperature as shown in the examples herein, specifically example4, and/or in the figures herein, specifically FIG. 83 . One embodimentof the present disclosure provides a crystalline Form XIII of AP1189cyclamate exhibiting a differential scanning calorimetry thermogramaccording to FIG. 83 . One embodiment of the present disclosure providesfor a crystalline Form XIII of AP1189 cyclamate exhibiting indifferential scanning calorimetry an onset temperature falling withinthe interval 141±7° C., such as 141±6° C., such as 141±5° C., such as141±4° C., such as 141±3° C., such as 141±2° C., such as 141±1° C.

One embodiment of the present disclosure provides for a crystalline FormXIV of AP1189 besylate exhibiting in differential scanning calorimetryan onset temperature between 219 and 223° C. One specific embodiment ofthe present disclosure provides a crystalline Form XIV of AP1189besylate exhibiting in differential scanning calorimetry an onsettemperature of substantially 216° C. In a further embodiment, the onsettemperature is assessed using a heating rate of 10° C./min. Oneembodiment of the disclosure provides for a crystalline Form XIV ofAP1189 besylate exhibiting in differential scanning calorimetry an onsettemperature as shown in the examples herein, specifically example 4,and/or in the figures herein, specifically FIG. 48 . One embodiment ofthe present disclosure provides a crystalline Form XIV of AP1189besylate exhibiting a differential scanning calorimetry thermogramaccording to FIG. 48 . One embodiment of the present disclosure providesfor a crystalline Form XIV of AP1189 besylate exhibiting in differentialscanning calorimetry an onset temperature falling within the interval216±7° C., such as 216±6° C., such as 216±5° C., such as 216±4° C., suchas 216±3° C., such as 216±2° C., such as 216±1° C.

One embodiment of the present disclosure provides for a crystalline FormXV of AP1189 oxalate exhibiting in differential scanning calorimetry apeak temperature between 204 and 218° C. One specific embodiment of thepresent disclosure provides a crystalline Form XV of AP1189 oxalateexhibiting in differential scanning calorimetry a peal temperature ofsubstantially 211° C. In a further embodiment, the peak temperature isassessed using a heating rate of 10° C./min. One embodiment of thedisclosure provides for a crystalline Form XV of AP1189 oxalateexhibiting in differential scanning calorimetry a peak temperature asshown in the examples herein, specifically example 4, and/or in thefigures herein, specifically FIG. 49 . One embodiment of the presentdisclosure provides a crystalline Form XV of AP1189 oxalate exhibiting adifferential scanning calorimetry thermogram according to FIG. 49 . Oneembodiment of the present disclosure provides for a crystalline Form XVof AP1189 oxalate exhibiting in differential scanning calorimetry a peaktemperature falling within the interval 211±7° C., such as 211±6° C.,such as 211±5° C., such as 211±4° C., such as 211±3° C., such as 211±2°C., such as 211±1° C.

One embodiment of the present disclosure provides for a crystalline FormXVI of AP1189 oxalate exhibiting in differential scanning calorimetry anonset temperature between 200 and 214° C. One specific embodiment of thepresent disclosure provides a crystalline Form XVI of AP1189 oxalateexhibiting in differential scanning calorimetry an onset temperature ofsubstantially 207° C. In a further embodiment, the onset temperature isassessed using a heating rate of 10° C./min. One embodiment of thedisclosure provides for a crystalline Form XVI of AP1189 oxalateexhibiting in differential scanning calorimetry an onset temperature asshown in the examples herein, specifically example 4, and/or in thefigures herein, specifically FIG. 50 . One embodiment of the presentdisclosure provides a crystalline Form XVI of AP1189 oxalate exhibitinga differential scanning calorimetry thermogram according to FIG. 50 .One embodiment of the present disclosure provides for a crystalline FormXVI of AP1189 oxalate exhibiting in differential scanning calorimetry anonset temperature falling within the interval 207±7° C., such as 207±6°C., such as 207±5° C., such as 207±4° C., such as 207±3° C., such as207±2° C., such as 207±1° C.

One embodiment of the disclosure provides for a crystalline Form XVII ofAP1189 oxalate exhibiting in differential scanning calorimetry an onsettemperature as shown in the examples herein, specifically example 4,and/or in the figures herein, specifically FIG. 51 . One embodiment ofthe present disclosure provides a crystalline Form XVII of AP1189oxalate exhibiting a differential scanning calorimetry thermogramaccording to FIG. 51 .

One embodiment of the present disclosure provides for a crystalline FormXVIII of AP1189 (+)-camphor-10-sulfonic acid exhibiting in differentialscanning calorimetry an onset temperature between 198 and 212° C. Onespecific embodiment of the present disclosure provides a crystallineForm XVIII of AP1189 (+)-camphor-10-sulfonic acid exhibiting indifferential scanning calorimetry an onset temperature of substantially205° C. In a further embodiment, the onset temperature is assessed usinga heating rate of 10° C./min. One embodiment of the disclosure providesfor a crystalline Form XVIII of AP1189 (+)-camphor-10-sulfonic acidexhibiting in differential scanning calorimetry an onset temperature asshown in the examples herein, specifically example 4, and/or in thefigures herein, specifically FIG. 52 . One embodiment of the presentdisclosure provides a crystalline Form XVIII of AP1189(+)-camphor-10-sulfonic acid exhibiting a differential scanningcalorimetry thermogram according to FIG. 52 . One embodiment of thepresent disclosure provides for a crystalline Form XVIII of AP1189(+)-camphor-10-sulfonic acid exhibiting in differential scanningcalorimetry an onset temperature falling within the interval 205±7° C.,such as 205±6° C., such as 205±5° C., such as 205±4° C., such as 205±3°C., such as 205±2° C., such as 205±1° C.

One embodiment of the present disclosure provides for a crystalline FormXIX of AP1189 oxoglutarate exhibiting in differential scanningcalorimetry an onset temperature between 74 and 88° C. One specificembodiment of the present disclosure provides a crystalline Form XIX ofAP1189 oxoglutarate exhibiting in differential scanning calorimetry anonset temperature of substantially 81° C. In a further embodiment, theonset temperature is assessed using a heating rate of 10° C./min. Oneembodiment of the disclosure provides for a crystalline Form XIX ofAP1189 oxoglutarate exhibiting in differential scanning calorimetry anonset temperature as shown in the examples herein, specifically example4, and/or in the figures herein, specifically FIG. 53 . One embodimentof the present disclosure provides a crystalline Form XIX of AP1189oxoglutarate exhibiting a differential scanning calorimetry thermogramaccording to FIG. 53 . One embodiment of the present disclosure providesfor a crystalline Form XIX of AP1189 oxoglutarate exhibiting indifferential scanning calorimetry an onset temperature falling withinthe interval 81±7° C., such as 81±6° C., such as 81±5° C., such as 81±4°C., such as 81±3° C., such as 81±2° C., such as 81±1° C.

One embodiment of the present disclosure provides for a crystalline FormXX of AP1189 DL-mandelic acid exhibiting in differential scanningcalorimetry an onset temperature between 103 and 117° C. One specificembodiment of the present disclosure provides a crystalline Form XX ofAP1189 DL-mandelic acid exhibiting in differential scanning calorimetryan onset temperature of substantially 110° C. In a further embodiment,the onset temperature is assessed using a heating rate of 10° C./min.One embodiment of the disclosure provides for a crystalline Form XX ofAP1189 DL-mandelic acid exhibiting in differential scanning calorimetryan onset temperature as shown in the examples herein, specificallyexample 4, and/or in the figures herein, specifically FIG. 54 . Oneembodiment of the present disclosure provides a crystalline Form XX ofAP1189 DL-mandelic acid exhibiting a differential scanning calorimetrythermogram according to FIG. 54 . One embodiment of the presentdisclosure provides for a crystalline Form XX of AP1189 DL-mandelic acidexhibiting in differential scanning calorimetry an onset temperaturefalling within the interval 110±7° C., such as 110±6° C., such as 110±5°C., such as 110±4° C., such as 1103° C., such as 1102° C., such as110±1° C.

One embodiment of the disclosure provides for a crystalline Form XXI ofAP1189 mandelic acid exhibiting in differential scanning calorimetry anonset temperature as shown in the examples herein, specifically example4, and/or in the figures herein, specifically FIG. 55 . One embodimentof the present disclosure provides a crystalline Form XXI of AP1189mandelic acid exhibiting a differential scanning calorimetry thermogramaccording to FIG. 55 .

One embodiment of the present disclosure provides for a crystalline FormXXII of AP1189 hippuric acid exhibiting in differential scanningcalorimetry an onset temperature between 132 and 146° C. One specificembodiment of the present disclosure provides a crystalline Form XXII ofAP1189 hippuric acid exhibiting in differential scanning calorimetry anonset temperature of substantially 139° C. In a further embodiment, theonset temperature is assessed using a heating rate of 10° C./min. Oneembodiment of the disclosure provides for a crystalline Form XXII ofAP1189 hippuric acid exhibiting in differential scanning calorimetry anonset temperature as shown in the examples herein, specifically example4, and/or in the figures herein, specifically FIG. 56 . One embodimentof the present disclosure provides a crystalline Form XXII of AP1189hippuric acid exhibiting a differential scanning calorimetry thermogramaccording to FIG. 56 . One embodiment of the present disclosure providesfor a crystalline Form XXII of AP1189 hippuric acid exhibiting indifferential scanning calorimetry an onset temperature falling withinthe interval 139±7° C., such as 139±6° C., such as 139±5° C., such as139±4° C., such as 1393° C., such as 1392° C., such as 139±1° C.

One embodiment of the present disclosure provides for a crystalline FormXXIII of AP1189 formate exhibiting in differential scanning calorimetryan onset temperature between 162 and 176° C. One specific embodiment ofthe present disclosure provides a crystalline Form XIII of AP1189formate exhibiting in differential scanning calorimetry an onsettemperature of substantially 169° C. In a further embodiment, the onsettemperature is assessed using a heating rate of 10° C./min. Oneembodiment of the disclosure provides for a crystalline Form XXIII ofAP1189 formate exhibiting in differential scanning calorimetry an onsettemperature as shown in the examples herein, specifically example 4,and/or in the figures herein, specifically FIG. 84 . One embodiment ofthe present disclosure provides a crystalline Form XXIII of AP1189formate exhibiting a differential scanning calorimetry thermogramaccording to FIG. 84 . One embodiment of the present disclosure providesfor a crystalline Form XXIII of AP1189 formate exhibiting indifferential scanning calorimetry an onset temperature falling withinthe interval 169±7° C., such as 169±6° C., such as 169±5° C., such as1694° C., such as 1693° C., such as 169±2° C., such as 169±1° C.

One embodiment of the present disclosure provides for a crystalline FormXXIV of AP1189 DL-lactic acid exhibiting in differential scanningcalorimetry an onset temperature between 182 and 196° C. One specificembodiment of the present disclosure provides a crystalline Form XXIV ofAP1189 DL-lactic acid exhibiting in differential scanning calorimetry anonset temperature of substantially 189° C. In a further embodiment, theonset temperature is assessed using a heating rate of 10° C./min. Oneembodiment of the disclosure provides for a crystalline Form XXIV ofAP1189 DL-lactic acid exhibiting in differential scanning calorimetry anonset temperature as shown in the examples herein, specifically example4, and/or in the figures herein, specifically FIG. 85 . One embodimentof the present disclosure provides a crystalline Form XXIV of AP1189DL-lactic acid exhibiting a differential scanning calorimetry thermogramaccording to FIG. 85 . One embodiment of the present disclosure providesfor a crystalline Form XXIV of AP1189 DL-lactic acid exhibiting indifferential scanning calorimetry an onset temperature falling withinthe interval 189±7° C., such as 189±6° C., such as 189±5° C., such as189±4° C., such as 189±3° C., such as 189±2° C., such as 189±1° C.

One embodiment of the present disclosure provides for a crystalline FormXXV of AP1189 DL-lactic acid exhibiting in differential scanningcalorimetry an onset temperature between 191 and 205° C. One specificembodiment of the present disclosure provides a crystalline Form XXV ofAP1189 DL-lactic acid exhibiting in differential scanning calorimetry anonset temperature of substantially 198° C. In a further embodiment, theonset temperature is assessed using a heating rate of 10° C./min. Oneembodiment of the disclosure provides for a crystalline Form XXV ofAP1189 DL-lactic acid exhibiting in differential scanning calorimetry anonset temperature as shown in the examples herein, specifically example4, and/or in the figures herein, specifically FIG. 86 . One embodimentof the present disclosure provides a crystalline Form XXV of AP1189DL-lactic acid exhibiting a differential scanning calorimetry thermogramaccording to FIG. 86 . One embodiment of the present disclosure providesfor a crystalline Form XXV of AP1189 DL-lactic acid exhibiting indifferential scanning calorimetry an onset temperature falling withinthe interval 198±7° C., such as 198±6° C., such as 198±5° C., such as198±4° C., such as 198±3° C., such as 198±2° C., such as 198±1° C.

One embodiment of the present disclosure provides for a crystalline FormXXVI of AP1189 glutaric acid exhibiting in differential scanningcalorimetry an onset temperature between 102 and 116° C. One specificembodiment of the present disclosure provides a crystalline Form XXVI ofAP1189 glutaric acid exhibiting in differential scanning calorimetry anonset temperature of substantially 109° C. In a further embodiment, theonset temperature is assessed using a heating rate of 10° C./min. Oneembodiment of the disclosure provides for a crystalline Form XXVI ofAP1189 glutaric acid exhibiting in differential scanning calorimetry anonset temperature as shown in the examples herein, specifically example4, and/or in the figures herein, specifically FIG. 87 . One embodimentof the present disclosure provides a crystalline Form XXVI of AP1189glutaric acid exhibiting a differential scanning calorimetry thermogramaccording to FIG. 87 . One embodiment of the present disclosure providesfor a crystalline Form XXVI of AP1189 glutaric acid exhibiting indifferential scanning calorimetry an onset temperature falling withinthe interval 109±7° C., such as 109±6° C., such as 109±5° C., such as109±4° C., such as 109±3° C., such as 109±2° C., such as 109±1° C.

One embodiment of the present disclosure provides for a crystalline FormXXVI of AP1189 glutaric acid exhibiting in differential scanningcalorimetry an onset temperature between 153 and 167° C. One specificembodiment of the present disclosure provides a crystalline Form XXVI ofAP1189 glutaric acid exhibiting in differential scanning calorimetry anonset temperature of substantially 160° C. In a further embodiment, theonset temperature is assessed using a heating rate of 10° C./min. Oneembodiment of the disclosure provides for a crystalline Form XXVI ofAP1189 glutaric acid exhibiting in differential scanning calorimetry anonset temperature as shown in the examples herein, specifically example4, and/or in the figures herein, specifically FIG. 87 . One embodimentof the present disclosure provides a crystalline Form XXVI of AP1189glutaric acid exhibiting a differential scanning calorimetry thermogramaccording to FIG. 87 . One embodiment of the present disclosure providesfor a crystalline Form XXVI of AP1189 glutaric acid exhibiting indifferential scanning calorimetry an onset temperature falling withinthe interval 160±7° C., such as 160±6° C., such as 160±5° C., such as160±4° C., such as 160±3° C., such as 160±2° C., such as 160±1° C.

One embodiment of the present disclosure provides for a crystalline FormXXVII of AP1189 glutaric acid exhibiting in differential scanningcalorimetry an onset temperature between 156 and 170° C. One specificembodiment of the present disclosure provides a crystalline Form XXVIIof AP1189 glutaric acid exhibiting in differential scanning calorimetryan onset temperature of substantially 163° C. In a further embodiment,the onset temperature is assessed using a heating rate of 10° C./min.One embodiment of the disclosure provides for a crystalline Form XXVIIof AP1189 glutaric acid exhibiting in differential scanning calorimetryan onset temperature as shown in the examples herein, specificallyexample 4, and/or in the figures herein, specifically FIG. 88 . Oneembodiment of the present disclosure provides a crystalline Form XXVIIof AP1189 glutaric acid exhibiting a differential scanning calorimetrythermogram according to FIG. 88 . One embodiment of the presentdisclosure provides for a crystalline Form XXVII of AP1189 glutaric acidexhibiting in differential scanning calorimetry an onset temperaturefalling within the interval 163±7° C., such as 163±6° C., such as 163±5°C., such as 163±4° C., such as 163±3° C., such as 163±2° C., such as163±1° C.

One embodiment of the present disclosure provides for a crystalline FormXXVIII of AP1189 glutaric acid exhibiting in differential scanningcalorimetry an onset temperature between 138 and 152° C. One specificembodiment of the present disclosure provides a crystalline Form XXVIIIof AP1189 glutaric acid exhibiting in differential scanning calorimetryan onset temperature of substantially 145° C. In a further embodiment,the onset temperature is assessed using a heating rate of 10° C./min.One embodiment of the disclosure provides for a crystalline Form XXVIIIof AP1189 glutaric acid exhibiting in differential scanning calorimetryan onset temperature as shown in the examples herein, specificallyexample 4, and/or in the figures herein, specifically FIG. 89 . Oneembodiment of the present disclosure provides a crystalline Form XXVIIIof AP1189 glutaric acid exhibiting a differential scanning calorimetrythermogram according to FIG. 89 . One embodiment of the presentdisclosure provides for a crystalline Form XXVIII of AP1189 glutaricacid exhibiting in differential scanning calorimetry an onsettemperature falling within the interval 145±7° C., such as 145±6° C.,such as 145±5° C., such as 145±4° C., such as 145±3° C., such as 145±2°C., such as 145±1° C.

One embodiment of the present disclosure provides for a crystalline FormXXVIII of AP1189 glutaric acid exhibiting in differential scanningcalorimetry an onset temperature between 153 and 167° C. One specificembodiment of the present disclosure provides a crystalline Form XXVIIIof AP1189 glutaric acid exhibiting in differential scanning calorimetryan onset temperature of substantially 160° C. In a further embodiment,the onset temperature is assessed using a heating rate of 10° C./min.One embodiment of the disclosure provides for a crystalline Form XXVIIIof AP1189 glutaric acid exhibiting in differential scanning calorimetryan onset temperature as shown in the examples herein, specificallyexample 4, and/or in the figures herein, specifically FIG. 89 . Oneembodiment of the present disclosure provides a crystalline Form XXVIIIof AP1189 glutaric acid exhibiting a differential scanning calorimetrythermogram according to FIG. 89 . One embodiment of the presentdisclosure provides for a crystalline Form XXVIII of AP1189 glutaricacid exhibiting in differential scanning calorimetry an onsettemperature falling within the interval 160±7° C., such as 160±6° C.,such as 160±5° C., such as 160±4° C., such as 160±3° C., such as 160±2°C., such as 160±1° C.

One embodiment of the present disclosure provides for a crystalline FormXXIX of AP1189 adipic acid exhibiting in differential scanningcalorimetry an onset temperature between 176 and 190° C. One specificembodiment of the present disclosure provides a crystalline Form XXIX ofAP1189 adipic acid exhibiting in differential scanning calorimetry anonset temperature of substantially 183° C. In a further embodiment, theonset temperature is assessed using a heating rate of 10° C./min. Oneembodiment of the disclosure provides for a crystalline Form XXIX ofAP1189 adipic acid exhibiting in differential scanning calorimetry anonset temperature as shown in the examples herein, specifically example4, and/or in the figures herein, specifically FIG. 90 . One embodimentof the present disclosure provides a crystalline Form XXIX of AP1189adipic acid exhibiting a differential scanning calorimetry thermogramaccording to FIG. 90 . One embodiment of the present disclosure providesfor a crystalline Form XXIX of AP1189 adipic acid exhibiting indifferential scanning calorimetry an onset temperature falling withinthe interval 183±7° C., such as 183±6° C., such as 183±5° C., such as183±4° C., such as 183±3° C., such as 183±2° C., such as 183±1° C.

The salts of AP1189 disclosed herein may be further identified by theirFT-IR spectra. FT-IR spectra may be obtained as outlined in Example 13.FT-IR are reported in peaks corresponding to specific wavenumbers givenin cm⁻¹. While the peaks are given herein with some degree of certainty,it is to be construed that the accuracy of an FT-IR measurement istypically ±1, ±2, or ±3 cm⁻¹. Accordingly, any peak reported herein isto be interpreted as having an accuracy of ±1, 2, or ±3 cm⁻¹.

One embodiment of the present disclosure provides for a crystalline FormIII of AP1189 napadisylate having an FT-IR as shown in FIG. 57 . Oneembodiment of the present disclosure provides for a crystalline Form IIIof AP1189 napadisylate having in an FT-IR spectrum peaks as shown inTable 45.

One embodiment of the present disclosure provides for a crystalline FormIV of AP1189 napadisylate having an FT-IR as shown in FIG. 58 . Oneembodiment of the present disclosure provides for a crystalline Form IVof AP1189 napadisylate having in an FT-IR spectrum peaks as shown inTable 46.

One embodiment of the present disclosure provides for a crystalline FormV of AP1189 esylate having an FT-IR as shown in FIG. 59 . One embodimentof the present disclosure provides for a crystalline Form V of AP1189esylate having in an FT-IR spectrum peaks as shown in Table 47.

One embodiment of the present disclosure provides for a crystalline FormVII of AP1189 edisylate having an FT-IR as shown in FIG. 60 . Oneembodiment of the present disclosure provides for a crystalline Form VIIof AP1189 edisylate having in an FT-IR spectrum peaks as shown in Table48.

One embodiment of the present disclosure provides for a crystalline FormVIII of AP1189 edisylate having an FT-IR as shown in FIG. 61 . Oneembodiment of the present disclosure provides for a crystalline FormVIII of AP1189 edisylate having in an FT-IR spectrum peaks as shown inTable 49.

One embodiment of the present disclosure provides for a crystalline FormIX of AP1189 edisylate having an FT-IR as shown in FIG. 62 . Oneembodiment of the present disclosure provides for a crystalline Form IXof AP1189 edisylate having in an FT-IR spectrum peaks as shown in Table50.

One embodiment of the present disclosure provides for a crystalline FormX of AP1189 nitrate having an FT-IR as shown in FIG. 63 . One embodimentof the present disclosure provides for a crystalline Form X of AP1189nitrate having in an FT-IR spectrum peaks as shown in Table 51.

One embodiment of the present disclosure provides for a crystalline FormXI of AP1189 cyclamate having an FT-IR as shown in FIG. 64 . Oneembodiment of the present disclosure provides for a crystalline Form XIof AP1189 cyclamate having in an FT-IR spectrum peaks as shown in Table52.

One embodiment of the present disclosure provides for a crystalline FormXII of AP1189 cyclamate having an FT-IR as shown in FIG. 65 . Oneembodiment of the present disclosure provides for a crystalline Form XIIof AP1189 cyclamate having in an FT-IR spectrum peaks as shown in Table53.

One embodiment of the present disclosure provides for a crystalline FormXIII of AP1189 cyclamate having an FT-IR as shown in FIG. 66 . Oneembodiment of the present disclosure provides for a crystalline FormXIII of AP1189 cyclamate having in an FT-IR spectrum peaks as shown inTable 54.

One embodiment of the present disclosure provides for a crystalline FormXIV of AP1189 besylate having an FT-IR as shown in FIG. 67 . Oneembodiment of the present disclosure provides for a crystalline Form XIVof AP1189 besylate having in an FT-IR spectrum peaks as shown in Table55.

One embodiment of the present disclosure provides for a crystalline FormXV of AP1189 oxalate having an FT-IR as shown in FIG. 68 . Oneembodiment of the present disclosure provides for a crystalline Form XVof AP1189 oxalate having in an FT-IR spectrum peaks as shown in Table56.

One embodiment of the present disclosure provides for a crystalline FormXVI of AP1189 oxalate having an FT-IR as shown in FIG. 69 . Oneembodiment of the present disclosure provides for a crystalline Form XVIof AP1189 oxalate having in an FT-IR spectrum peaks as shown in Table57.

One embodiment of the present disclosure provides for a crystalline FormXVII of AP1189 oxalate having an FT-IR as shown in FIG. 70 . Oneembodiment of the present disclosure provides for a crystalline FormXVII of AP1189 oxalate having in an FT-IR spectrum peaks as shown inTable 58.

One embodiment of the present disclosure provides for a crystalline FormXVIII of AP1189 (+)-camphor-10-sulfonic acid having an FT-IR as shown inFIG. 71 . One embodiment of the present disclosure provides for acrystalline Form XVIII of AP1189 (+)-camphor-10-sulfonic acid having inan FT-IR spectrum peaks as shown in Table 59.

One embodiment of the present disclosure provides for a crystalline FormXIX of AP1189 oxoglutarate having an FT-IR as shown in FIG. 72 . Oneembodiment of the present disclosure provides for a crystalline Form XIXof AP1189 oxoglutarate having in an FT-IR spectrum peaks as shown inTable 60.

One embodiment of the present disclosure provides for a crystalline FormXX of AP1189 DL-mandelic acid having an FT-IR as shown in FIG. 73 . Oneembodiment of the present disclosure provides for a crystalline Form XXof AP1189 DL-mandelic acid having in an FT-IR spectrum peaks as shown inTable 61.

One embodiment of the present disclosure provides for a crystalline FormXXI of AP1189 DL-mandelic acid having an FT-IR as shown in FIG. 74 . Oneembodiment of the present disclosure provides for a crystalline Form XXIof AP1189 DL-mandelic acid having in an FT-IR spectrum peaks as shown inTable 62.

One embodiment of the present disclosure provides for a crystalline FormXXII of AP1189 hippuric acid having an FT-IR as shown in FIG. 75 . Oneembodiment of the present disclosure provides for a crystalline FormXXII of AP1189 hippuric acid having in an FT-IR spectrum peaks as shownin Table 63.

One embodiment of the present disclosure provides for a crystalline FormXXIII of AP1189 formate having an FT-IR as shown in FIG. 76 . Oneembodiment of the present disclosure provides for a crystalline FormXXIII of AP1189 formate having in an FT-IR spectrum peaks as shown inTable 64.

One embodiment of the present disclosure provides for a crystalline FormXXIV of AP1189 DL-lactic acid having an FT-IR as shown in FIG. 77 . Oneembodiment of the present disclosure provides for a crystalline FormXXIV of AP1189 DL-lactic acid having in an FT-IR spectrum peaks as shownin Table 65.

One embodiment of the present disclosure provides for a crystalline FormXXV of AP1189 DL-lactic acid having an FT-IR as shown in FIG. 78 . Oneembodiment of the present disclosure provides for a crystalline Form XXVof AP1189 DL-lactic acid having in an FT-IR spectrum peaks as shown inTable 66.

One embodiment of the present disclosure provides for a crystalline FormXXVI of AP1189 glutaric acid having an FT-IR as shown in FIG. 79 . Oneembodiment of the present disclosure provides for a crystalline FormXXVI of AP1189 glutaric acid having in an FT-IR spectrum peaks as shownin Table 67.

One embodiment of the present disclosure provides for a crystalline FormXXVII of AP1189 glutaric acid having an FT-IR as shown in FIG. 80 . Oneembodiment of the present disclosure provides for a crystalline FormXXVII of AP1189 glutaric acid having in an FT-IR spectrum peaks as shownin Table 68.

One embodiment of the present disclosure provides for a crystalline FormA of AP1189 acetic acid having an IR spectrum as shown in FIG. 92 .

Properties of Crystalline Forms

The present disclosure provides salts of AP1189 having highersolubility. It is to be construed that when solubility is discussed inthe context of the present disclosure, solubility in aqueous solution ispreferably meant. In one embodiment of the disclosure, solubility is inaqueous medium. Specifically, as shown in the examples herein, thecrystalline Form A of AP1189 acetate was found to have a high solubilityat pH 1.2. Likewise, crystalline Form B of AP1189 succinate was found tohave a higher solubility at pH 1.2-1.3. It is an object of the presentdisclosure to provide salts of AP1189 having a high solubility at lowpH, as this improves in vivo uptake of AP1189 after administration to asubject, such as oral administration to a subject.

High solubility of AP1189 salts is not a given, as is shown in theexamples herein. For example, both AP1189 tosylate and AP1189 fumaratewere found to have low solubility at low pH, e.g. pH 1.2-1.3.

One embodiment of the present disclosure provides for a salt of AP1189having a solubility at pH 1.2 of at least 10 mM, such as least 15 mM,such as at least 20 mM, such as at least 25 mM, such as at least 30 mM,such as at least 35 mM.

One embodiment of the present disclosure provides for a crystalline FormA of AP1189 acetate having a solubility at pH 1.2 of at least 100 mM,such as at least 110 mM, such as at least 120 mM.

One embodiment of the present disclosure provides for a crystalline FormB of AP1189 succinate having a solubility at pH 1.2 of at least 20 mM,such as at least 25 mM, such as at least 30 mM, such as at least 35 mM.

The solubility of a compound may be assessed by adding a surplus of thecompound to a volume of solvent such that some of the compound is notdissolved, then isolating the non-dissolved compound and measuring theamount. The solubility of a compound may alternatively be assessed byadding a surplus of the compound to a volume of solvent such that someof the compound is not dissolved, and then measure the amount ofcompound in solution. Measuring the amount of compound in solution maybe done using any suitable method, such as HPLC, titration, orspectrometry.

Methods for Preparing AP1189 Salts

Salts of AP1189 may be prepared as disclosed herein.

One embodiment of the present disclosure provides for a method ofproducing AP1189 acetate of crystalline Form A, said method comprising:

-   -   i. mixing AP1189 and acetic acid in a solvent to form a mixture;        and    -   ii. isolating the AP1189 acetate of crystalline Form A from said        mixture.

As used herein, “mixture” can mean a solution or a slurry of one or moresolids in a solvent or mixture of solvents. In one embodiment of thedisclosure, the mixture is a solution, where the solute or solutes aresubstantially fully dissolved. In one embodiment, the mixture is aslurry, wherein one or more solutes are only partly dissolved, and theremaining part or parts of the solute or solutes are not dissolved.

One embodiment of the present disclosure provides for a method forproducing AP1189 acetate of crystalline Form A, said method comprising:

-   -   i. mixing AP1189 and acetate salt in a solvent to form a        mixture; and    -   ii. isolating the AP1189 acetate of crystalline Form A from said        mixture.

In one embodiment, the acetate salt is ammonium acetate or a metalacetate salt such as sodium acetate, lithium acetate, magnesium acetate,potassium acetate, or calcium acetate.

In one embodiment, the method further comprises adding an acid in stepi, such as an organic acid or a mineral acid.

One embodiment of the disclosure provides for a method for producingAP1189 acetate of crystalline Form A, said method comprising:

-   -   i. mixing AP1189 acetate in a solvent to form a composition; and    -   ii. isolating the AP1189 acetate of crystalline Form A from said        composition.

In one embodiment, such method is effective in converting AP1189 acetatenot of crystalline Form A to AP1189 acetate of crystalline Form A.

As used herein, “composition” can mean a solution or a slurry of onesolid in a solvent or mixture of solvents. In one embodiment of thedisclosure, the composition is a solution, where the solute issubstantially fully dissolved. In one embodiment, the composition is aslurry, wherein the solute is only partly dissolved, and the remainingpart of the solute is not dissolved. The composition may furthercomprise one or more other agents or reagents which may be dissolved ormay be only partly dissolved. Such other agents includes, but are notlimited to, surfactants, detergents, acids, bases, sugars, salts,biomolecules, bioactive agents, and other excipients such aspharmaceutical excipients.

This present disclosure also relates to non-solid compositions, e.g.liquid compositions, gel compositions, pastes, creams, or ointmentsprepared from the crystalline forms disclosed herein. One embodimentprovides for a liquid composition, gel composition, paste, cream, orointment prepared from a crystalline form disclosed herein. One specificembodiment provides for a liquid composition prepared from a crystallineform disclosed herein and a solvent. In a specific embodiment, thesolvent is aqueous. In one embodiment, the present disclosure providesfor a method of preparing a liquid composition, a gel composition, apaste, a cream, or an ointment, said method comprising mixing acrystalline form disclosed herein and one or more additional agents. Onespecific embodiment provides for a method of preparing a liquidcomposition, said method comprising mixing a crystalline form disclosedherein and a solvent. In a further embodiment, the solvent is aqueous.

One embodiment of the disclosure provides for a method for producingN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumacetate of crystalline Form A, said method comprising:

-   -   i. mixing 3-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl]-propanal, amino        guanidine or a salt thereof, and acetic acid or a salt thereof        in a solvent, and    -   ii. isolating the        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        acetate of crystalline Form A from said composition.

Any one of the above agents of step i may be generated from a precursorin situ.

One embodiment of the present disclosure provides for a method forproducingN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumacetate of crystalline Form A, said method comprising:

-   -   i. providing        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine        or an        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        salt,    -   ii. introducing acetate as a counter ion using ion exchange, and    -   iii. isolating        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        acetate of crystalline Form A.

One embodiment of the present disclosure provides for a method ofproducing AP1189 succinate of crystalline Form B, said methodcomprising:

-   -   i. mixing AP1189 and succinic acid in a solvent to form a        mixture; and    -   ii. isolating the AP1189 succinate of crystalline Form B from        the mixture.

One embodiment of the present disclosure provides for a method ofproducing AP1189 succinate of crystalline Form B, said methodcomprising:

-   -   i. mixing a AP1189 salt and succinic acid in a solvent to form a        mixture, and    -   ii. isolating the AP1189 succinate of crystalline Form B from        the mixture.

One embodiment of the present disclosure provides for a method forproducing theN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsuccinate of crystalline Form B, said method comprising:

-   -   i. mixing 3-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl]-propanal, amino        guanidine or a salt thereof, and succinic acid or a salt thereof        in a solvent, and    -   ii. isolating the        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        succinate of crystalline Form B from said composition.

Any one of the above agents of step i may be generated from a precursorin situ.

One embodiment of the present disclosure provides for a method forproducing theN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsuccinate of crystalline Form B, said method comprising:

-   -   i. providing        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine        or an        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        salt,    -   ii. introducing succinate as a counter ion using ion exchange,        and    -   iii. isolating        N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinium        succinate of crystalline Form B.

In one embodiment of the present disclosure, the solvent is a protic ora polar aprotic solvent. In one embodiment, the solvent is selected fromthe group consisting of 1,4-dioxane, methanol, ethanol, 1-propanol,2-propanol, acetone, acetonitrile, anisole, isopropyl acetate,methylethyl ketone, water, and ethyl acetate.

In one embodiment of the present disclosure, the mixture or thecomposition is heated at least once before the isolating step. In oneembodiment, the mixture or the composition is heated and cooled incycles before the isolation step. In one embodiment, the mixture or thecomposition is heated and cooled in cycles for up to 72 hours before theisolating step. In one embodiment the mixture or the composition isheated and cooled in cycles for 15 min to 72 hours before the isolatingstep. In one embodiment, one cycle comprises heating the mixture or thecomposition to at least a first threshold temperature, maintaining thetemperature above said first threshold temperature for a first duration,then cooling the mixture or the composition to below a second thresholdtemperature and maintaining the temperature below said second thresholdtemperature for a second duration. In one embodiment of the presentdisclosure, the cycle is carried out 1 to 200 times. In one embodimentof the present disclosure, the first threshold temperature is 30° C.,such as 35° C., such as 40° C., such as 45° C., such as 50° C., such as55° C., such as 60° C., such as 65° C., such as 70° C., such as 75° C.,such as 80° C. In one embodiment of the present disclosure, the secondthreshold temperature is 30° C., such as 25° C., such as 20° C., such as15° C., such as 10° C., such as 7° C., such as 5° C. In one embodimentof the present disclosure, the first and/or the second duration is 1 to2 min, such as 2 to 5 min, such as 5 to 10 min, such as 10 to 20 min,such as 20 to 30 min, such as 30 to 40 min, such as 40 to 50 min, suchas 50 to 60 min, such as 1 hour to 1.5 hours, such as 1.5 to 2 hours,such as 2 to 3 hours, such as 3 to 4 hours, such as 4 to 5 hours, suchas 5 to 6 hours, such as 6 to 7 hours, such as 7 to 8 hours. In oneembodiment, the first and the second durations are the same. In oneembodiment, the first and the second durations are different. In oneembodiment, the first duration is different or the same for each cycle.In one embodiment, the second duration is different or the same for eachcycle.

In one embodiment, heating is to about 40° C.

In one embodiment, cooling is to about 20° C.

In one embodiment, the method further comprises a step of adding ananti-solvent to the mixture or the composition before the isolationstep. In one embodiment, the anti-solvent is a non-polar aproticsolvent. In one embodiment, the anti-solvent is selected from the groupconsisting of tert-butyl methyl ether, THF, and acetone, and mixturescomprising tert-butyl methyl ether, THF, or acetone. In one embodimentof the present disclosure, the anti-solvent is water.

Isolation of crystals may be carried out using an appropriate means. Inone embodiment of the disclosure, the isolation is carried out usingfiltration, centrifugation, and/or evaporation of the solvent orsolvents. In one embodiment, a slow evaporation method is utilised. Inone embodiment, a fast evaporation method is utilised. In oneembodiment, the evaporation is carried out using spray drying. In oneembodiment, the evaporation is carried out using fluid bed drying,freeze drying, vacuum drying, tumble drying, rotary evaporation, and/orthin-film evaporation. In one embodiment, the drying is carried outusing a conductive (contact) dryer, including tray dryers, rotary conedryers, tumble dryers, and paddle dryers. In one further embodiment, thedrying is carried out using a carrier gas.

In one embodiment of the present disclosure, one or more pKa values,such as at least one pKa, of the corresponding acid to the counter ionof the AP1189 salt is about equal to or lower than the pKa value ofsuccinic acid and/or acetic acid. By way of example, “the correspondingacid to the counter ion of the AP1189 fumarate” is fumaric acid. The pKavalue of acetic acid is 4.756. The pKa value corresponding to the firstacid dissociation of succinic acid is 4.2. The pKa value correspondingto the second acid dissociation of succinic acid is 5.6. Accordingly, inone embodiment, the pKa value of the corresponding acid to the counterion of the AP1189 salt is about equal to or lower than 4.756. In anotherembodiment, the pKa value of the corresponding acid to the counter ionof the AP1189 salt is about equal to or lower than 4.2 and/or 5.6.

One embodiment of the present disclosure provides for a crystalline FormA of AP1189 acetate produced by the method as disclosed herein.

One embodiment of the present disclosure provides for a crystalline FormB of AP1189 succinate produced by the method as disclosed herein.

One embodiment of the present disclosure provides for a method ofproducing crystalline Form A of AP1189 acetate as disclosed herein,wherein the method further comprises adding a seed crystal ofcrystalline Form A of AP1189 acetate before the isolation step. Oneembodiment of the present disclosure provides for a method of producingcrystalline Form B of AP1189 succinate as disclosed herein, wherein themethod further comprises adding a seed crystal of crystalline Form B ofAP1189 succinate before the isolation step.

Pharmaceutical Compositions

One embodiment of the disclosure provides for a pharmaceuticalcomposition comprising the crystalline Form A of AP1189 acetate asdisclosed herein and a pharmaceutically acceptable excipient.

One embodiment of the disclosure provides for a pharmaceuticalcomposition comprising the crystalline Form B of AP1189 succinate asdisclosed herein and a pharmaceutically acceptable excipient.

In some embodiments there is provided an oral formulation, apharmaceutical composition, or unit dosage form comprising thecrystalline Form A of AP1189 acetate as disclosed herein or thecrystalline Form B of AP1189 succinate as disclosed herein.

One embodiment provides for a pharmaceutical composition as disclosedherein, wherein the pharmaceutical composition is formulated for oraladministration. Such composition may be in the form of a tablet or acapsule.

One embodiment of the disclosure provides for a method of preparing apharmaceutical composition comprising mixing the crystalline Form A ofAP1189 acetate with a pharmaceutically acceptable excipient.

One embodiment of the disclosure provides for a method of preparing apharmaceutical composition comprising mixing the crystalline Form B ofAP1189 succinate with a pharmaceutically acceptable excipient.

One embodiment of the disclosure provides for the crystalline Form A ofAP1189 acetate, the crystalline Form B of AP1189 succinate, or thepharmaceutical composition as disclosed herein for use in medicine. Oneembodiment of the present disclosure provides for the crystalline Form Aof AP1189 acetate, the crystalline Form B of AP1189 succinate, or thepharmaceutical composition as disclosed herein, for use in the treatmentof a kidney disease such as proteinuria, a cardiovascular disease, anarthritic disease, or a viral infection.

One embodiment of the present disclosure provides for a method oftreating a disease or disorder in a subject in need thereof, said methodcomprising administering crystalline Form A of AP1189 acetate,crystalline Form B of AP1189 succinate, or the pharmaceuticalcomposition as disclosed herein, to a subject in need thereof. In onefurther embodiment, the disease or disorder is selected from the listconsisting of a kidney disease such as proteinuria, a cardiovasculardisease, an arthritic disease, or a viral infection.

One embodiment of the present disclosure provides for a use of thecrystalline Form A of AP1189 acetate or the crystalline Form B of AP1189succinate, or the pharmaceutical composition as disclosed herein for themanufacture of a medicament for treatment of a disease or disorder.

Medical Use

It is an aspect of the present disclosure to provide a pharmaceuticalformulation, such as an oral formulation, comprising the crystallineForm A of AP1189 acetate as disclosed herein or the crystalline Form Bof AP1189 succinate as disclosed herein, for use in the treatment of adisease or disorder.

In some embodiments, the disease or disorder is selected from the groupconsisting of a kidney disease, an arthritic disease, a viral disease ordisorder, and a cardiovascular disease and/or atherosclerosis.

Kidney Disease

It is an aspect of the present disclosure to provide a pharmaceuticalformulation such as an oral formulation, a pharmaceutical composition,or unit dosage form according to the present disclosure for use intreating or preventing a kidney disease.

Also disclosed is a method of treating or preventing a kidney disease ina subject in need thereof, wherein the subject is administered atherapeutically effect amount of the oral formulation, pharmaceuticalcomposition, or unit dosage form of the present disclosure.

Also disclosed is the use of an oral formulation, pharmaceuticalcomposition, or unit dosage form according to the present disclosure foruse in the manufacture of a medicament for the treatment or preventionof a kidney disease.

In some embodiments of the present disclosure there is provided an oralformulation, such as a solid oral formulation, comprising thecrystalline form A of AP1189 acetate or the crystalline Form B of AP1189succinate, and at least one pharmaceutically acceptable excipient, asdisclosed herein, for use in treating or preventing a kidney disease.

In some embodiments said kidney disease present with proteinuria. Insome embodiments said kidney disease is a proteinuric kidney disease.

In some embodiments said kidney disease is a glomerular disease

In some embodiments said kidney disease is nephrotic syndrome(glomerulonephrosis).

In some embodiments said kidney disease is primary nephrotic syndrome(primary glomerulonephrosis).

In some embodiments said primary nephrotic syndrome is membranousglomerulonephritis (MGN) (or membranous nephropathy (MN)).

In some embodiments said primary nephrotic syndrome is focal segmentalglomerulosclerosis (FSGS).

In some embodiments said primary nephrotic syndrome ismembranoproliferative glomerulonephritis (MPGN) (mesangiocapillaryglomerulonephritis).

In some embodiments said membranoproliferative glomerulonephritis (MPGN)is selected from Type 1 MPGN and Type 2 MPGN.

In some embodiments said primary nephrotic syndrome is rapidlyprogressive glomerulonephritis (RPGN) (crescentic GN).

In some embodiments said primary nephrotic syndrome is minimal changedisease (MCD).

In some embodiments said kidney disease is secondary nephrotic syndrome(secondary glomerulonephrosis).

In some embodiments said secondary nephrotic syndrome is caused by anunderlying autoimmune disease, an underlying cancer disease, anunderlying genetic disorder, or by an underlying disease selected fromthe group consisting of: Systemic lupus erythematosus (SLE), Diabeticnephropathy, Sarcoidosis, Sjögren's syndrome, Amyloidosis, Multiplemyeloma, Vasculitis, Cancer and Genetic disorders (such as congenitalnephrotic syndrome).

In some embodiments said secondary nephrotic syndrome is caused byDiabetic nephropathy, by an infection, such as a urinary tractinfection, such as an infection selected from the group consisting ofHIV, syphilis, hepatitis such as hepatitis A, B and C,post-streptococcal infection, urinary schistosomiasis and Ebola. In someembodiments said secondary nephrotic syndrome is drug-induced.

In some embodiments said kidney disease is an inflammatory kidneydisease.

In some embodiments said kidney disease is glomerulonephritis (GN). Insome embodiments said glomerulonephritis is selected from the groupconsisting of IgA nephropathy (Berger's disease), IgM nephropathy,Post-infectious glomerulonephritis and Thin basement membrane disease.

In some embodiment said kidney disease is idiopathic membranousnephropathy (iMN).

In some embodiments there is provided an oral formulation, apharmaceutical composition, or unit dosage form according to the presentdisclosure for use in treating or preventing idiopathic membranousnephropathy (iMN).

Arthritic Disease

It is as aspect of the present disclosure to provide an oralformulation, a pharmaceutical composition, or unit dosage form accordingto the present disclosure for use in treating or preventing an arthriticdisease.

Also disclosed is a method of treating or preventing an arthriticdisease in a subject in need thereof, wherein the subject isadministered a therapeutically effect amount of the oral formulation,pharmaceutical composition, or unit dosage form of the presentdisclosure.

Also disclosed is the use of an oral formulation, pharmaceuticalcomposition, or unit dosage form according to the present disclosure foruse in the manufacture of a medicament for the treatment or preventionof an arthritic disease.

In some embodiments of the present disclosure there is provided an oralformulation, such as a solid oral formulation, comprising thecrystalline Form A of AP1189 acetate or crystalline Form B of AP1189succinate, and at least one pharmaceutically acceptable excipient, asdisclosed herein, for use in treating or preventing an arthriticdisease.

In one embodiment the arthritic disease is an auto-immune disease and/oran inflammatory disease that presents with joint inflammation.

In one embodiment, the arthritic disease is selected from the groupconsisting of inflammatory arthritis, degenerative arthritis, metabolicarthritis, reactive arthritis and infectious arthritis.

In one embodiment, the arthritic disease is inflammatory arthritis.

In one embodiment, the inflammatory arthritis is selected from the groupconsisting of Rheumatoid Arthritis (RA), Psoriatic Arthritis, andAnkylosing Spondylitis.

In one embodiment, the inflammatory arthritis is Rheumatoid Arthritis(RA).

In one embodiment, the rheumatoid arthritis is severe active RA(CDAI>22). In one embodiment, the rheumatoid arthritis is RA with aCDAI>22.

In one embodiment, the rheumatoid arthritis is RA with a DAS28 score ofabove 5.1.

In one embodiment, the rheumatoid arthritis is juvenile rheumatoidarthritis (JRA).

In one embodiment, the degenerative arthritis is osteoarthritis.

In one embodiment, the metabolic arthritis is gouty arthritis.

In one embodiment, the reactive and/or infectious arthritis is arthritisassociated with infection with one or more of Hepatitis C, Chlamydia,gonorrhoea, salmonella or shigella.

In one embodiment the arthritic disease is arthritis as part of asystemic inflammatory disease.

In one embodiment, the arthritis as part of a systemic inflammatorydisease, such as an inflammatory disease selected from the groupconsisting of systemic lupus erythematosus, mixed connective tissuedisease, Still's disease, and Polymyalgia Rheumatica.

In some embodiments there is provided an oral formulation, apharmaceutical composition, or unit dosage form according to the presentdisclosure for use in treating or preventing rheumatoid arthritis.

In some embodiments there is provided an oral formulation, apharmaceutical composition, or unit dosage form according to the presentdisclosure in combination with MTX (methotrexate) for use in treating orpreventing rheumatoid arthritis.

In some embodiments there is provided an oral formulation, apharmaceutical composition, or unit dosage form according to the presentdisclosure, alone or in combination with MTX (methotrexate), for use intreating or preventing rheumatoid arthritis in patients with aninappropriate response to MTX (such as patients with a reduced responseto MTX treatment, such as an MTX non-responder).

Viral Disease or Disorder

It is as aspect of the present disclosure to provide an oralformulation, a pharmaceutical composition, or unit dosage form accordingto the present disclosure for use in treating or preventing a viraldisease or disorder.

Also disclosed is a method of treating or preventing a viral disease ordisorder in a subject in need thereof, wherein the subject isadministered a therapeutically effect amount of the oral formulation,pharmaceutical composition, or unit dosage form of the presentdisclosure.

Also disclosed is the use of an oral formulation, pharmaceuticalcomposition, or unit dosage form according to the present disclosure foruse in the manufacture of a medicament for the treatment or preventionof a viral disease or disorder.

In some embodiments of the present disclosure there is provided an oralformulation, such as a solid oral formulation, comprising apharmaceutically acceptable salt of AP1189, such as AP1189 acetate orAP1189 succinate, and at least one pharmaceutically acceptableexcipient, as disclosed herein, for use in treating or preventing aviral disease or disorder.

In some embodiments said viral disease or disorder is a symptomaticviral disease or disorder.

In some embodiments said viral disease or disorder is a symptomaticviral disease or disorder with inflammation, such as hyperinflammation.

In some embodiments said viral disease or disorder is a symptomaticviral disease or disorder with inflammation, such as hyperinflammation,in one or more organs.

Inflammation in one or more organs may also be referred to as localinflammation.

In some embodiments said one or more organs are selected from the groupconsisting of lungs, the respiratory tract, kidney, liver, pancreas,spleen, exocrine glands, endocrine glands, lymph nodes, brain, heart,muscles, bone marrow, skin, skeleton, bladder, reproduction organsincluding the phallopian tubes, eye, ear, vascular system, thegastrointestinal tract including small intestines, colon, rectum,canalis analis and the prostate gland.

In some embodiments said viral disease or disorder is inflammatory viraldiseases or disorders.

In some embodiments said viral disease or disorder is a viralrespiratory infection, such as a viral lower respiratory infection.

In some embodiments said viral disease or disorder is viral respiratorydiseases or disorders.

In some embodiments said viral disease or disorder is viral diseases ordisorders of the lung.

In some embodiments said viral disease or disorder is viral diseases ordisorders with inflammation in the respiratory system, such as in thelungs and/or respiratory tract.

In some embodiments said viral disease or disorder is viral diseases ordisorders with one or more respiratory symptoms. In one embodiment saidone or more respiratory symptoms are selected from the group consistingof cough, dry cough, dyspnea, impaired oxygenation, respiratory illness,respiratory dysfunction, respiratory failure, respiratory syndrome andacute respiratory disease (ARD).

In some embodiments said viral disease or disorder is severe disease.Severe disease present with dyspnoea, increased respiratory frequency,reduced blood oxygen saturation and/or lung infiltrates.

In some embodiments said viral disease or disorder is critical disease.Critical disease present with respiratory failure, septic shock, and/ormultiple organ dysfunction (MOD) or multiple organ failure (MOF).

In some embodiments said viral disease or disorder is viral pneumonia.

In some embodiments said viral disease or disorder is viralbronchiolitis.

In some embodiments said viral disease or disorder is viral diseases ordisorders with respiratory failure.

In some embodiments said viral disease or disorder is acute respiratorydistress syndrome (ARDS).

In some embodiments said viral disease or disorder is viral acuterespiratory distress syndrome (ARDS).

In some embodiments said viral disease or disorder is symptomaticCOVID-19 with acute respiratory distress syndrome (ARDS).

In some embodiments there is provided an oral formulation, apharmaceutical composition, or unit dosage form according to the presentdisclosure for use in treating or preventing ARDS, such as viral ARDS.

In some embodiments said viral disease or disorder is viral diseases anddisorders with systemic inflammatory distress syndrome (SIDS) and/orsepsis.

In some embodiments said viral disease or disorder is viral diseases anddisorders with pulmonary insufficiency.

In some embodiments said viral disease or disorder is viral diseases ordisorders with cytokine release syndrome (CRS) and/or a cytokine storm(hypercytokinemia).

In some embodiments said viral disease or disorder is caused by a viralinfection selected from the group consisting of Severe Acute RespiratorySyndrome CoronaVirus 2 (SARS-CoV-2), often referred to as the COVID-19virus; SARS-CoV, MERS-CoV, the dengue virus and influenza virus(including Type A, Type B and Type C).

Cardiovascular Disease and/or Atherosclerosis

It is as aspect of the present disclosure to provide an oralformulation, a pharmaceutical composition, or unit dosage form accordingto the present disclosure for use in treating or preventing acardiovascular disease and/or atherosclerosis.

Also disclosed is a method of treating or preventing a cardiovasculardisease and/or atherosclerosis in a subject in need thereof, wherein thesubject is administered a therapeutically effect amount of the oralformulation, pharmaceutical composition, or unit dosage form of thepresent disclosure.

Also disclosed is the use of an oral formulation, pharmaceuticalcomposition, or unit dosage form according to the present disclosure foruse in the manufacture of a medicament for the treatment or preventionof a cardiovascular disease and/or atherosclerosis.

In some embodiments of the present disclosure there is provided an oralformulation, such as a solid oral formulation, comprising thecrystalline Form A of AP1189 acetate as disclosed herein or thecrystalline Form B of AP1189 succinate as disclosed herein, and at leastone pharmaceutically acceptable excipient, as disclosed herein, for usein treating or preventing a cardiovascular disease and/oratherosclerosis.

In some embodiments said cardiovascular disease is selected from thegroup consisting of coronary artery diseases (CAD) such as angina andmyocardial infarction (commonly known as a heart attack); stroke, heartfailure, hypertensive heart disease, rheumatic heart disease,cardiomyopathy, abnormal heart rhythms, congenital heart disease,valvular heart disease, carditis, aortic aneurysms, peripheral arterydisease, vascular disease, thromboembolic disease, and venousthrombosis.

In some embodiments said cardiovascular disease is atheroscleroticcardiovascular disease.

In some embodiments said atherosclerotic cardiovascular disease isselected from the group consisting of coronary artery disease, stroke(cerebrovascular disease), and peripheral artery disease.

In some embodiments said cardiovascular disease is vascularinflammation.

Systemic Inflammatory Disorders

It is as aspect of the present disclosure to provide an oralformulation, a pharmaceutical composition, or unit dosage form accordingto the present disclosure for use in treating or preventing a systemicinflammatory disorder.

Also disclosed is a method of treating or preventing a systemicinflammatory disorder in a subject in need thereof, wherein the subjectis administered a therapeutically effective amount of the oralformulation, pharmaceutical composition, or unit dosage form of thepresent disclosure.

Also disclosed is the use of an oral formulation, pharmaceuticalcomposition, or unit dosage form according to the present disclosure foruse in the manufacture of a medicament for the treatment or preventionof a systemic inflammatory disorder.

In some embodiments of the present disclosure there is provided an oralformulation, such as a solid oral formulation, comprising thecrystalline Form A of AP1189 acetate as disclosed herein or thecrystalline Form B of AP1189 succinate, and at least onepharmaceutically acceptable excipient, as disclosed herein, for use intreating or preventing a systemic inflammatory disorder.

Systemic disorders with possible involvement of the nervous systeminclude a variety of diseases with presumed inflammatory and autoimmunepathomechanisms, among them Behçet disease, sarcoidosis, systemic lupuserythematosus, juvenile idiopathic arthritis, scleroderma, and Sjögrensyndrome. This disease group encompasses systemic inflammatory disorderswith a genetically defined dysregulation of the innate immune system aswell as systemic autoimmune disorders characterized by alterations ofthe adaptive immunity such as autoantibodies and autoreactive T cells.

In some embodiments said systemic inflammatory disorder is an autoimmunedisorder.

In some embodiments said systemic inflammatory disorder is selected fromthe group consisting of Behçet disease, sarcoidosis, systemic lupuserythematosus, juvenile idiopathic arthritis, scleroderma, Sjögrensyndrome, myositis including dermamyositis and polymyositis, vasculitis,giant cell arteritis, ankylosing spondylitis, polymyalgia rheumatic andpsoriatic arthritis.

EXAMPLES Example 1: Formation of Salts

From the Reaction YieldingN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine

An acid is added as a slurry or solution in a protic or polar aproticsolvent to a heated slurry or solution of3-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl]-propanal and aminoguanidine or asalt thereof in a protic or polar aprotic solvent. The resulting mixtureis heated and stirred, preferably until completion of the reaction,before cooled and optionally an anti-solvent, such as a non-polaraprotic solvent, is added. The resulting salt is isolated byconventional methods, such as filtration, centrifugation, evaporation ofthe solvents, including spray drying.

From Free Base

An acid is added (such as an excess of said acid) as a slurry orsolution in a protic or polar aprotic solvent to a slurry ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine in aprotic or polar aprotic solvent. The resulting mixture is heated andcooled in cycles between 15 min and 72 hours, before cooled andoptionally an anti-solvent, such as a non-polar aprotic solvent, isadded. The resulting salt is isolated by conventional methods, such asfiltration, centrifugation, evaporation of the solvents, including spraydrying.

From Another Salt

This method is feasible if the corresponding acid to the counterion isstronger in the salt formed. An excess of an acid is added as a slurryor solution in a protic or polar aprotic solvent to a slurry ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalt in a protic or polar aprotic solvent. The resulting mixture isheated and cooled in cycles between 15 min and 72 hours, before cooledand optionally an anti-solvent, such as a non-polar aprotic solvent, isadded. The resulting salt is isolated by conventional methods, such asfiltration, centrifugation, or evaporation of the solvents, includingspray drying.

Exemplary Procedure for Formation of Acetate Salt

0.9 equivalent of acetic acid was slowly whilst stirring added to3-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl]-propanal and aminoguanidinehydrogen carbonate in ethanol. Heated at 50-55° C. for 1 hour beforeadditional 0.11 equivalent acetic acid was added and the mixture washeated to reflux for at least 2 hours. The suspension was cooled to 60°C. before tert-butyl methyl ether was added. Cooled and kept at 2-5° C.for 10-16 hours. Filtered and washed with tert-butyl methyl ether,before recrystallized from ethanol.

The procedure produces a polymorph of AP1189 acetate salt correspondingto XRPD pattern 1.

Exemplary Procedure for Formation of Succinate Salt of AP1189

2-propanol:water 90:10 v/v was added to AP1189 acetate to prepare aslurry. 2-propanol:water 90:10 v/v was added to 1.1 equivalents ofsuccinic acid. The counterion slurry was added to the acetate saltslurry. Temperature cycling was carried out between ambient and 40° C.for ca. 18 h with 4 hour hold periods at ambient temperature and 4 hourhold periods at 40° C. The entire slurry was then isolated by Buchnerfiltration and washed with deionised water. The solids were dried undervacuum at ambient.

The procedure produced a polymorph of AP1189 succinate saltcorresponding to XRPD pattern 1.

Salt Break of Freebase AP1189

Ethyl acetate and 1 M sodium bicarbonate was added to AP1190 acetate tocreate a biphasic mixture. The mixture was transferred to a separatingfunnel and the aqueous phase was removed. The organic phase was washedwith water. The organic phase was dried with sodium sulphate. Thesolvent of the organic phase was removed by rotary evaporation.

The procedure produced AP1189 freebase as a solid.

Example 2: Polymorphism Assessment for AP1189 Acetate Salt

Methods

A polymorphism assessment was carried out in order to identify alternatepolymorphs of AP1189 acetate: AP1189 acetate was dissolved in1,4-dioxane-water and lyophilized to obtain an amorphous solid. Aliquotswere suspended in the specific solvents and heated in temperature cyclesbetween ambient and 40° C. for 3 days, before being isolated byfiltration.

Results

Table 2 outlines the results of the polymorphism study. Acetate Pattern1 was obtained from 8 solvent systems. A mixture of Pattern 1 and 2 wasobtained from 8 solvent systems. Pattern 3 was obtained from THF.Extended temperature cycling for a further 3 days for the acetatePattern 1 and 2 mixture from ethyl acetate resulted in conversion toacetate Pattern 1.

TABLE 2 Results from polymorphism study. Solvent or solvent system XRPDanalysis 1,4-Dioxane Pattern 1 1-Butanol Gum 1-Propanol Gum 2-Methyl THFPattern 1 and 2 2-Propanol Pattern 1 90% 2-Propanol:10% Water (% v/v)Gum Acetone Pattern 1 Acetonitrile Pattern 1 Anisole Pattern 1Dichloromethane Pattern 1 and 2 Di-isopropyl ether Gum 3%Dimethylsulfoxide:97% THF (% v/v) Solution Ethanol Gum Ethyl AcetatePattern 1 and 2* Heptane Pattern 1 and 2 Isopropyl Acetate Pattern 1 11%Methanol:89% t-BME (% v/v) Gum Methylethyl Ketone Pattern 1Methylisobutyl Ketone Pattern 1 and 2 14% N,N′-Dimethylacetamide:86%t-BME (% v/v) Pattern 1 and 2 tert-Butyl methyl ether Pattern 1 and 2Tetrahydrofuran Pattern 3 Toluene Pattern 1 and 2 Water Pattern 1*Extended temperature cycling for a further 3 days for the acetatePattern 1 and 2 mixture from ethyl acetate resulted in conversion toacetate Pattern 1.

Conclusion

The polymorphism study for AP1189 acetate revealed three differentpolymorphs, corresponding to XRPD Pattern 1, Pattern 1 and 2 (i.e.Pattern 2 as a mixture with Pattern 1), and Pattern 3.

Example 3: X-Ray Powder Diffraction

Methods

XRPD analysis was carried out on a PANalytical X'pert pro with PIXceldetector (128 channels), scanning the samples between 3 and 35° 2θ. Thematerial was gently ground (where required) to release any agglomeratesand loaded onto a multi-well plate with Kapton or Mylar polymer film tosupport the sample. The multi-well plate was then placed into thediffractometer and analysed using Cu K radiation (α1 λ=1.54060 Å;α2=1.54443 Å; p=1.39225 Å; α1:α2 ratio=0.5) running in transmission mode(step size 0.0130° 2θ, step time 18.87 s) using 40 kV/40 mA generatorsettings.

Results

AP1189 Acetate Form A

The XRPD diffractogram for AP1189 acetate salt Pattern 1 crystallisedfrom acetonitrile is shown in FIG. 1 . The corresponding XRPDdiffractogram peak list for acetate Pattern 1 is shown in Table 3.

TABLE 3 XRPD diffractogram peak list for acetate Pattern 1 fromacetonitrile. Pos. Height FWHM Left d-spacing Rel. Int. [°2θ] [cts][°2θ] [Å] [%] 6.0782 61.99 0.0768 14.54111 3.01 11.4999 376.76 0.07687.69497 18.27 11.7129 266.97 0.0895 7.55551 12.94 12.1877 173.70 0.08957.26219 8.42 12.9668 297.55 0.0512 6.82756 14.43 15.4892 966.17 0.05125.72091 46.85 15.6424 2062.40 0.0768 5.66523 100.00 15.8752 681.440.0768 5.58267 33.04 16.2455 289.74 0.0640 5.45625 14.05 18.3417 132.310.0640 4.83712 6.42 18.5685 91.14 0.0768 4.77856 4.42 19.5716 316.980.0895 4.53584 15.37 20.0451 546.76 0.1023 4.42976 26.51 20.5722 265.470.1151 4.31743 12.87 21.1229 532.99 0.1151 4.20611 25.84 21.5003 272.410.0895 4.13312 13.21 21.8494 142.83 0.0895 4.06787 6.93 22.3320 305.940.0895 3.98103 14.83 23.5498 1324.22 0.1279 3.77786 64.21 24.77521187.85 0.1151 3.59371 57.60 25.7239 208.72 0.1279 3.46328 10.12 26.96251300.30 0.1151 3.30693 63.05 27.4977 285.23 0.0768 3.24378 13.83 28.1563198.27 0.0895 3.16939 9.61 28.5405 90.88 0.1279 3.12758 4.41 30.211366.51 0.1023 2.95832 3.22 30.7262 58.06 0.1279 2.90991 2.82 31.2143198.84 0.0768 2.86551 9.64 32.2538 40.40 0.2047 2.77549 1.96 32.885929.42 0.1535 2.72357 1.43 33.4037 43.22 0.2047 2.68254 2.10 34.335617.97 0.2047 2.61183 0.87 Characteristic peaks are indicated in bold.Indexed unit cell data: a [Å] 7.8; b [Å] 15.1; c [Å] 20.7; alpha [°]73.6; beta [°] 80.5; gamma [°] 86.5; volume [Å³] 2311.8.

AP1189 Acetate Form I

The XRPD diffractogram for AP1189 acetate salt Pattern 1 and 2crystallised from ethyl acetate is shown in FIG. 2 . The correspondingXRPD diffractogram peak list for acetate salt Pattern 1 and 2 is shownin Table 4.

TABLE 4 XRPD diffractogram peak list for acetate Pattern 1 and 2 fromethyl acetate. Pos. Height FWHM Left d-spacing Rel. Int. [°2θ] [cts][°2θ] [Å] [%] 3.2635 158.25 0.6140 27.07331 6.65 5.7636 129.03 0.051215.33407 5.42 11.5242 491.32 0.1023 7.67882 20.64 11.7039 436.17 0.06407.56130 18.32 12.1439 260.95 0.1023 7.28832 10.96 12.9022 494.37 0.08956.86160 20.76 14.7250 397.68 0.0768 6.01607 16.70 14.9424 1114.74 0.12795.92902 46.82 15.3955 2380.95 0.0768 5.75554 100.00 15.6099 1481.010.0640 5.67694 62.20 15.8562 467.40 0.0895 5.58931 19.63 16.2700 306.750.1279 5.44809 12.88 16.4491 241.34 0.0768 5.38917 10.14 16.7354 143.360.1023 5.29761 6.02 18.0224 665.00 0.0895 4.92210 27.93 18.3450 141.430.0768 4.83626 5.94 18.5587 133.47 0.0768 4.78105 5.61 18.9146 118.410.0895 4.69189 4.97 19.5667 272.77 0.1279 4.53697 11.46 19.9482 633.370.0624 4.44737 26.60 19.9955 663.36 0.0384 4.44065 27.86 20.1366 348.130.0640 4.40985 14.62 20.4922 248.29 0.1535 4.33412 10.43 21.0979 338.620.1279 4.21103 14.22 21.4992 410.08 0.1023 4.13333 17.22 21.7757 380.770.1279 4.08146 15.99 22.4413 550.91 0.0768 3.96190 23.14 22.7456 183.390.1023 3.90958 7.70 23.2063 330.75 0.1279 3.83300 13.89 23.5430 2355.440.1279 3.77893 98.93 24.2404 2157.44 0.1151 3.67177 90.61 24.7492 788.300.1023 3.59742 33.11 25.3486 189.70 0.0768 3.51371 7.97 25.7030 227.220.1023 3.46606 9.54 26.5363 135.18 0.0768 3.35907 5.68 26.9149 1479.120.1407 3.31268 62.12 27.5238 407.92 0.1023 3.24076 17.13 28.1364 363.050.0512 3.17158 15.25 28.6315 98.86 0.1535 3.11786 4.15 28.9219 125.280.1023 3.08720 5.26 30.1919 39.10 0.1535 2.96018 1.64 30.6694 51.020.2558 2.91516 2.14 31.1058 142.84 0.1279 2.87525 6.00 32.3303 18.510.2047 2.76910 0.78 33.2416 39.67 0.3070 2.69524 1.67 33.8884 21.890.2047 2.64527 0.92 Characteristic peaks are indicated in bold.

AP1189 Acetate Form II

The XRPD diffractogram for AP1189 acetate salt Pattern 3 crystallisedfrom THF is shown in FIG. 3 . The corresponding XRPD diffractogram peaklist for acetate salt Pattern 3 is shown in Table 5.

TABLE 5 XRPD diffractogram peak list for acetate Pattern 3 from THF.Pos. Height FWHM Left d-spacing Rel. Int. [°2θ] [cts] [°2θ] [Å] [%]7.4087 420.49 0.1023 11.93253 11.02 7.5476 521.50 0.0640 11.71324 13.679.3630 615.90 0.0895 9.44578 16.15 10.2795 148.14 0.0768 8.60560 3.8810.3817 145.57 0.0640 8.52114 3.82 12.7834 3086.55 0.0768 6.92512 80.9312.8920 1547.27 0.0384 6.86699 40.57 13.2514 3226.07 0.0895 6.6815784.58 13.5704 569.08 0.0512 6.52520 14.92 14.1812 647.30 0.0768 6.2454916.97 14.8366 334.40 0.1279 5.97104 8.77 15.1355 499.98 0.0384 5.8538113.11 15.3087 614.19 0.1023 5.78798 16.10 15.5117 478.34 0.0895 5.7126812.54 16.0316 1497.51 0.0895 5.52858 39.26 16.3925 709.43 0.1023 5.4076318.60 17.0466 862.25 0.1023 5.20159 22.61 17.2943 190.95 0.0768 5.127655.01 17.6910 274.54 0.0895 5.01355 7.20 18.2222 208.88 0.0895 4.868575.48 18.4583 387.60 0.0640 4.80685 10.16 18.8043 1265.02 0.1407 4.7191733.17 19.5046 902.38 0.0895 4.55128 23.66 19.6774 1113.67 0.0640 4.5117029.20 19.7852 1009.94 0.0512 4.48735 26.48 20.2727 758.58 0.1023 4.3805419.89 21.1079 3814.09 0.1023 4.20907 100.00 21.4406 1810.10 0.10234.14449 47.46 21.8531 1509.72 0.1151 4.06719 39.58 22.0123 1816.880.0895 4.03813 47.64 22.3192 771.07 0.1535 3.98330 20.22 22.7104 1217.980.0895 3.91555 31.93 23.0558 2438.93 0.1151 3.85768 63.95 23.3224 694.420.0768 3.81417 18.21 23.6146 902.32 0.1279 3.76763 23.66 23.9023 235.450.1023 3.72293 6.17 24.5581 544.77 0.0768 3.62499 14.28 25.0512 717.520.0768 3.55474 18.81 25.4354 261.30 0.2047 3.50191 6.85 26.0711 205.720.1023 3.41795 5.39 26.6312 908.25 0.0780 3.34455 23.81 26.6726 949.130.0512 3.34222 24.88 26.9412 646.78 0.1279 3.30951 16.96 27.2272 315.930.0895 3.27539 8.28 27.6284 279.23 0.1535 3.22872 7.32 27.8687 183.380.1023 3.20144 4.81 28.3712 268.31 0.1791 3.14586 7.03 28.6345 398.220.1023 3.11753 10.44 29.3348 503.54 0.0640 3.04468 13.20 29.7178 312.610.1023 3.00631 8.20 30.2079 657.53 0.1535 2.95865 17.24 30.5905 188.330.0768 2.92251 4.94 30.9427 286.22 0.1791 2.89004 7.50 31.9648 186.600.1279 2.79992 4.89 33.1436 281.81 0.1535 2.70299 7.39 33.6247 136.290.1535 2.66540 3.57 34.5747 173.57 0.128 2.59431 4.55 Characteristicpeaks are indicated in bold. Indexed unit cell data: a [Å] 12.5; b [Å]12.7; c [Å] 20.9; alpha [°] 76.0; beta [°] 73.1; gamma [°] 86.6; volume[Å³] 3074.1.

AP1189 Tosylate Form C

The XRPD diffractogram for AP1189 tosylate salt Pattern 1 crystallisedfrom methanol is shown in FIG. 4 . The corresponding XRPD diffractogrampeak list for tosylate salt Pattern 1 is shown in Table 6.

TABLE 6 XRPD diffractogram peak list for tosylate Pattern 1 frommethanol. Pos. Height FWHM Left d-spacing Rel. Int. [°2θ] [cts] [°2θ][Å] [%] 7.95280 565.46 0.0768 11.11733 13.44 9.42330 1279.54 0.08959.38555 30.41 9.96040 1509.46 0.0895 8.88062 35.88 10.76630 133.520.0768 8.21756 3.17 12.07190 246.37 0.0640 7.33164 5.86 12.31920 203.440.0640 7.18500 4.84 13.44230 2110.32 0.0895 6.58708 50.16 14.090601043.18 0.0768 6.28546 24.80 14.49790 4207.16 0.1023 6.10978 100.0015.28210 833.29 0.1023 5.79797 19.81 15.70980 713.17 0.0895 5.6410616.95 15.98490 2747.52 0.1023 5.54462 65.31 16.74560 1838.99 0.10235.29441 43.71 17.55870 1963.25 0.1535 5.05103 46.66 19.15130 708.390.1151 4.63442 16.84 19.79500 1554.81 0.1023 4.48515 36.96 20.010101455.65 0.1151 4.43743 34.60 20.74200 698.27 0.1023 4.28247 16.6020.98000 3263.54 0.1279 4.23443 77.57 21.34790 1658.88 0.1279 4.1622939.43 22.02470 407.91 0.1151 4.03589 9.70 22.38540 763.27 0.0640 3.9716718.14 22.65840 400.17 0.0384 3.92442 9.51 22.83650 258.14 0.0768 3.894216.14 23.14460 310.98 0.1279 3.84307 7.39 23.55690 160.13 0.1279 3.776743.81 24.05140 646.06 0.1023 3.70020 15.36 24.29100 327.31 0.1023 3.664247.78 25.15830 4097.87 0.1151 3.53984 97.40 25.43100 1927.26 0.11513.50250 45.81 25.70240 416.16 0.1023 3.46613 9.89 26.05180 374.86 0.10233.42043 8.91 26.65210 421.78 0.1791 3.34474 10.03 27.13070 158.43 0.15353.28682 3.77 27.66440 258.67 0.0895 3.22461 6.15 28.07950 526.46 0.08953.17788 12.51 29.04430 391.90 0.1023 3.07448 9.32 29.24250 336.72 0.03843.05409 8.00 29.88270 587.69 0.1023 2.99009 13.97 30.28370 319.89 0.23032.95141 7.60 30.67120 509.33 0.1535 2.91500 12.11 31.39270 66.82 0.20472.84963 1.59 32.74010 194.37 0.1279 2.73537 4.62 33.15360 274.41 0.17912.70220 6.52 33.52400 157.80 0.1791 2.67318 3.75 34.06450 185.09 0.12792.63200 4.40 34.63470 112.70 0.1535 2.58996 2.68 Characteristic peaksare indicated in bold.

AP1189 Fumarate Form D

The XRPD diffractogram for AP1189 fumarate salt Pattern 1 crystallisedfrom isopropylalcohol:water 90:10 v/v is shown in FIG. 5 . Thecorresponding XRPD diffractogram peak list for fumarate salt Pattern 1from isopropylalcohol:water 90:10 v/v is shown in Table 7.

TABLE 7 XRPD diffractogram peak list for fumarate Pattern 1 fromisopropylalcohol:water 90:10 v/v. Pos. Height FWHM Left d-spacing Rel.Int. [°2θ] [cts] [°2θ] [Å] [%] 8.6209 310.50 0.0640 10.25719 6.33 9.22961873.51 0.0895 9.58209 38.22 10.2345 347.27 0.0640 8.64332 7.08 10.5354852.43 0.0640 8.39713 17.39 10.9191 1388.14 0.0768 8.10292 28.32 11.47282930.97 0.0895 7.71311 59.80 11.8926 2170.42 0.0895 7.44176 44.2813.3718 346.23 0.0512 6.62169 7.06 15.7963 1426.98 0.1023 5.61039 29.1116.0311 849.53 0.0895 5.52872 17.33 16.3575 561.06 0.1023 5.41913 11.4516.5708 474.42 0.0768 5.34985 9.68 17.2941 531.10 0.0640 5.12771 10.8417.5600 3319.60 0.1023 5.05067 67.73 18.1912 548.58 0.0895 4.87682 11.1918.5329 529.75 0.0512 4.78765 10.81 18.6734 794.04 0.0895 4.75195 16.2019.4122 1637.66 0.1023 4.57272 33.41 19.5565 1187.94 0.0512 4.5393224.24 19.7714 359.40 0.0640 4.49046 7.33 20.5917 692.05 0.0512 4.3133814.12 21.1710 4901.56 0.1279 4.19667 100.00 21.3706 1056.31 0.07684.15791 21.55 21.9494 2839.37 0.1407 4.04957 57.93 22.6944 230.40 0.10233.91828 4.70 23.0753 363.82 0.0895 3.85446 7.42 23.4284 1295.19 0.14073.79716 26.42 23.8881 2543.55 0.1535 3.72511 51.89 24.5122 1525.500.1535 3.63167 31.12 24.7719 401.96 0.0768 3.59418 8.20 25.0387 542.090.1151 3.55649 11.06 26.0822 1360.04 0.1279 3.41652 27.75 26.34174606.74 0.1407 3.38345 93.99 26.9772 178.54 0.0900 3.30243 3.64 27.5829462.97 0.1023 3.23395 9.45 27.9868 874.09 0.1023 3.18819 17.83 28.5342442.65 0.1151 3.12826 9.03 28.7849 321.79 0.1023 3.10159 6.57 29.1336199.54 0.1279 3.06525 4.07 29.5204 318.82 0.0640 3.02597 6.50 29.9470467.63 0.0895 2.98382 9.54 30.2812 204.98 0.1535 2.95165 4.18 30.97141155.91 0.1404 2.88504 23.58 31.0214 1083.09 0.0624 2.88766 22.1031.5455 443.03 0.2808 2.83383 9.04 31.9500 514.93 0.0780 2.79887 10.5132.4106 193.90 0.1872 2.76014 3.96 33.0815 204.69 0.1248 2.70568 4.1833.5275 415.89 0.0936 2.67070 8.48 34.2307 89.28 0.1872 2.61743 1.8234.7358 407.34 0.0468 2.58051 8.31 Characteristic peaks are indicated inbold.

AP1189 Succinate Form B

The XRPD diffractogram for AP1189 succinate salt Pattern 1 crystallisedfrom isopropanol:water 90:10 v/v is shown in FIG. 6 . The correspondingXRPD diffractogram peak list for succinate salt Pattern 1 is shown inTable 8.

TABLE 8 XRPD diffractogram peak list for succinate Pattern 1 fromisopropanol:water 90:10 v/v. Pos. Height FWHM Left d-spacing Rel. Int.[°2θ] [cts] [°2θ] [Å] [%]  5.4069 986.93 0.0640 16.34500  48.23  9.71782046.18  0.0768 9.10169 100.00  12.2493 579.97 0.0895 7.22581 28.3412.6625 194.49 0.0768 6.99096  9.50 13.3815 1060.24  0.0895 6.6168851.82 13.6088  85.82 0.0768 6.50687  4.19 15.7849 670.53 0.1023 5.6144232.77 16.2820 940.26 0.1023 5.44410 45.95 18.0910  90.94 0.1023 4.90360 4.44 18.6109 131.29 0.1023 4.76776  6.42 18.9143  81.96 0.0895 4.69198 4.01 19.5146 976.30 0.1023 4.54897 47.71 19.8650 251.71 0.0895 4.4695212.30 21.1182  76.58 0.1279 4.20703  3.74 21.7806 623.87 0.0624 4.0771830.49 21.8237 575.40 0.0468 4.07934 28.12 21.9659 346.03 0.0624 4.0432116.91 22.1773 283.42 0.1092 4.00514 13.85 22.3520 227.12 0.0936 3.9742311.10 22.7669 1214.56  0.1404 3.90274 59.36 23.4039  80.68 0.15603.79793  3.94 23.7400  51.39 0.0936 3.74492  2.51 24.6205 235.25 0.10923.61295 11.50 24.9667 183.96 0.0624 3.56363  8.99 25.2780 236.68 0.14043.52044 11.57 26.0672  79.01 0.1872 3.41562  3.86 26.2812 115.48 0.09363.38830  5.64 26.7189 1090.24  0.1404 3.33377 53.28 27.4666 226.040.0936 3.24470 11.05 28.5058 649.21 0.1560 3.12872 31.73 29.0947 167.430.1560 3.06673  8.18 29.4393  71.92 0.1560 3.03161  3.51 30.0230  19.050.3744 2.97398  0.93 31.5076  74.16 0.1560 2.83715  3.62 32.3204 158.750.2496 2.76763  7.76 32.7195  60.07 0.1248 2.73478  2.94 33.5540  65.220.1872 2.66865  3.19 34.1457  52.21 0.5616 2.62374  2.55 Characteristicpeaks are indicated in bold.

AP1189 Napadisylate Form III

The XRPD diffractogram for AP1189 napadisylate salt Pattern 1crystallised from 2-propanol:water 90:10% v/v is shown in FIG. 14 . Thecorresponding XRPD diffractogram peak list for napadisylate salt Pattern1 is shown in Table 9.

TABLE 9 XRPD diffractogram peak list for napadisylate Pattern 1 from2-propanol:water 90:10% v/v. Pos. [°2θ] d-spacing [Å] Height [cts] Rel.Int. [%]  7.5504 11.70884  689.5  18.85  10.7197 8.2532  944.25 25.82 12.3794 7.1502  1041.08  28.46  13.4473 6.58465 1775.32  48.54  13.97766.33602 516.26 14.11  15.0881 5.87208 1507.82  41.22  15.5452 5.700431428.49  39.06  17.1935 5.15749 578.34 15.81  18.2562 4.8596  147.084.02 18.7653 4.72888 105.22 2.88 19.2562 4.60944 116.02 3.17 20.33084.36815 344.81 9.43 21.3564 4.16064 180.29 4.93 21.7571 4.08153 255.626.99 22.1571 4.01206 3657.63  100    22.8309 3.89516 1110.18  30.35 23.4703 3.79047 1179.36  32.24  24.3345 3.65778 425.24 11.63  24.904 3.57542 341.67 9.34 25.3384 3.5151  356.8  9.76 26.817  3.32455 2133.99 58.34  27.1283 3.28439 217.11 5.94 27.6015 3.22914 261.56 7.15 27.97443.18957 1458.18  39.87  28.5214 3.12964 329.01 9.00 28.9049 3.08898129.88 3.55 29.4676 3.03126 159.64 4.36 29.9117 2.98727 132.26 3.6230.4558 2.93512 173.56 4.75 31.3597 2.85019  60.18 1.65 31.8567 2.80918261.91 7.16 32.5624 2.74989  58.95 1.61 33.4807 2.67654  56.16 1.54Characteristic peaks are indicated in bold.

AP1189 Napadisylate Form IV

The XRPD diffractogram for AP1189 napadisylate salt Pattern 2crystallised from THF is shown in FIG. 15 . The corresponding XRPDdiffractogram peak list for napadisylate salt Pattern 2 is shown inTable 10.

TABLE 10 XRPD diffractogram peak list for napadisylate Pattern 2 fromTHF. Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%]  5.428616.27965  346.5  79.53  6.5128 13.56063   14.65  3.36  7.4311 11.89657  47.58 10.92  8.5219 10.37613  163.19 37.46 10.0575 8.7878   35.75  8.2110.8271 8.17155 104.41 23.97 11.3074 7.81909  58.98 13.54 12.06557.32943  70.52 16.19 12.5500 7.05339 242.28 55.61 13.1311 6.7425  159.5 36.61 15.5722 5.6906  435.67 100    16.2658 5.44496 141.14 32.4  16.61425.33158 109.83 25.21 18.3509 4.83472 301.22 69.14 19.0496 4.65509 92.921.32 19.4848 4.55586 195.31 44.83 19.8774 4.46675 193.35 44.38 20.25854.37995 158.03 36.27 21.0620 4.21813 219.31 50.34 22.0067 4.03915 314.6572.22 22.7195 3.91401 259.61 59.59 23.3676 3.8069  367.37 84.32 24.19613.67839 303.55 69.67 25.1931 3.53212 169.22 38.84 25.8383 3.44821 292.4467.13 26.8947 3.31512 155.27 35.64 30.4999 2.92856  25.88  5.94Characteristic peaks are indicated in bold.

AP1189 Esylate Form V

The XRPD diffractogram for AP1189 esylate salt Pattern 1 crystallisedfrom methylethyl ketone is shown in FIG. 16 . The corresponding XRPDdiffractogram peak list for esylate salt Pattern 1 is shown in Table 11.

TABLE 11 XRPD diffractogram peak list for esylate Pattern 1 frommethylethyl ketone. Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%] 8.4696 10.44008  96.34 47.64 9.813 9.01365 125.06  61.84 10.42038.48969 99.32 49.11 11.331  7.80283 29.09 14.39 11.5369 7.66404 26.9813.34 12.9606 6.82518 30.38 15.02 14.3275 6.17693 62.18 30.75 14.53016.09631 200.81  99.29 15.3453 5.77425 76.71 37.93 16.5381 5.36036202.23  100    18.639  4.76065 175.44  86.75 19.7148 4.50323 125.45 62.03 20.1181 4.41384 174.51  86.29 20.9895 4.22902 74.36 36.77 21.12374.20595 83.32 41.2  21.9184 4.05521 76.71 37.93 22.4735 3.9563  80.8439.97 23.9411 3.71699 58.21 28.78 25.514  3.48841 36.26 17.93 26.05643.41702 74.49 36.83 26.4224 3.3705  46.97 23.23 26.7682 3.3305  111.98 55.37 27.5072 3.24   35.01 17.31 29.7173 3.00387 10.74  5.31 31.41222.84555 22.93 11.34 32.1715 2.7801  16.17  8.00 33.501  2.67275 24.3512.04 Characteristic peaks are indicated in bold.

AP1189 Edisylate Form VI

The XRPD diffractogram for AP1189 edisylate salt Pattern 1 crystallisedfrom 2-Propanol:water (80:20% v/v) is shown in FIG. 17 . Thecorresponding XRPD diffractogram peak list for edisylate salt Pattern 1is shown in Table 12.

TABLE 12 XRPD diffractogram peak list for edisylate Pattern 1 from2-Propanol:water (80:20 %v/v). Pos. [°2θ] d-spacing [Å] Height [cts]Rel. Int. [%]  4.7606 18.56231  1152.22  94.52  9.5373 9.27355 445.5736.55 10.8586 8.14796 233.5  19.16 11.603  7.62679 126.33 10.36 12.78766.92285 908.15 74.5  14.2703 6.2067  250.78 20.57 15.2286 5.81822 339.8227.88 16.4938 5.37466 1218.96  100    16.976  5.21876  97.95  8.0417.8605 4.96636 561.86 46.09 18.5957 4.77162 419.86 34.44 19.18314.62683 215.67 17.69 20.2602 4.38322 273.24 22.42 21.4287 4.14676 516.3642.36 22.4944 3.95267 481.25 39.48 23.4349 3.79612 624.9  51.27 24.47753.63674 376.83 30.91 25.2503 3.52716 478.62 39.26 25.4765 3.49346 234.8 19.26 26.4673 3.36767 160.37 13.16 27.167  3.28251 506.76 41.57 28.04173.17944  76.44  6.27 29.4833 3.02968 120.53  9.89 29.7204 3.00357 71.2 5.84 30.1891 2.96045 157.41 12.91 30.9905 2.88569 105.44  8.65 32.58862.74774  59.41  4.87 33.3411 2.68743  98.37  8.07 34.2969 2.61252  25.44 2.09 Characteristic peaks are indicated in bold.

AP1189 Edisylate Form VII

The XRPD diffractogram for AP1189 edisylate salt Pattern 2 crystallisedfrom methylethyl ketone is shown in FIG. 18 . The corresponding XRPDdiffractogram peak list for edisylate salt Pattern 2 is shown in Table13.

TABLE 13 XRPD diffractogram peak list for edisylate Pattern 2 frommethylethyl ketone. Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%] 6.0662 14.56989  1499.14  71.99 10.0241 8.82426 358.32 17.21 11.74357.53586 730.04 35.06 12.0936 7.31848 994.92 47.78 12.7392 6.94906 586  28.14 14.1325 6.26692 281.25 13.51 15.7281 5.63457 2082.36  100   16.2886 5.43741  73.51  3.53 17.6463 5.02614 139.37  6.69 17.93694.94129 119.4   5.73 18.3429 4.83683 256.13 12.3  19.2641 4.60756 739.7435.52 20.1215 4.41311 922.85 44.32 20.893  4.25186 304.45 14.62 21.75464.08539 1293.59  62.12 22.3549 3.97702 230.14 11.05 22.7399 3.91055531.54 25.53 23.6495 3.76216 1405.44  67.49 24.2528 3.66992 299.01 14.3624.825  3.58662 279.37 13.42 25.1151 3.54584 413   19.83 25.7826 3.45553230.5  11.07 26.5375 3.35893 317.73 15.26 27.0339 3.29837 200.04  9.6127.4795 3.2432  119.71  5.75 28.2254 3.16178 267.76 12.86 28.61253.11988 326.38 15.67 29.6505 3.01298 123.96  5.95 30.5784 2.92363 141.586.8 31.2303 2.86408 184.2   8.85 31.8981 2.80331  50.64  2.43 32.42132.76154  98.58  4.73 32.8959 2.72277  69.53  3.34 33.53  2.6705   24.941.2 34.1437 2.6239   13.62  0.65 Characteristic peaks are indicated inbold.

AP1189 Edisylate Form VIII

The XRPD diffractogram for AP1189 edisylate salt Pattern 4 crystallisedfrom THF is shown in FIG. 19 . The corresponding XRPD diffractogram peaklist for edisylate salt Pattern 4 is shown in Table 14.

TABLE 14 XRPD diffractogram peak list for edisylate Pattern 4 from THF.Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%]  6.4465 13.71127 191.95 14.27  9.9098 8.92585 71.5  5.32 12.145  7.28767 583.39 43.3812.4961 7.07778 129.05 9.6 12.9954 6.81261 368.87 27.43 14.0381 6.30364112.5   8.37 15.4892 5.72092 1344.79  100    17.7793 4.98886 229.2717.05 18.2552 4.85583  85.69  6.37 18.6687 4.75313 171.63 12.76 19.54324.53863 215.92 16.06 20.0215 4.43494 373.31 27.76 20.6977 4.29155 760.3456.54 21.672  4.10076 591.86 44.01 22.2098 3.99935 256.17 19.05 23.123 3.84661 356.78 26.53 24.1173 3.69023 405.74 30.17 25.23  3.52996 365.3727.17 25.6746 3.46695 126.18  9.38 27.0992 3.29057  76.34  5.68 27.91983.19305  16.88  1.26 30.6998 2.91235  54.54  4.06 31.0943 2.87391  70.76 5.26 31.6385 2.82571  50.08  3.72 34.4866 2.59859  31.14  2.32Characteristic peaks are indicated in bold.

AP1189 Edisylate Form IX

The XRPD diffractogram for AP1189 edisylate salt Pattern 5 crystallisedfrom 2-Propanol:water (80:20% v/v) is shown in FIG. 20 . Thecorresponding XRPD diffractogram peak list for edisylate salt Pattern 5is shown in Table 15.

TABLE 15 XRPD diffractogram peak list for edisylate Pattern 5 from2-Propanol:water (80:20 % v/v). Pos. [°2θ] d-spacing [Å] Height [cts]Rel. Int. [%]  4.4981 19.645   792.29 100    8.987 9.84018 198.33 25.0311.701  7.55689  88.54 11.17 12.1573 7.28032 254.63 32.14 12.36857.15054 124.48 15.71 13.098  6.75385  29.04  3.67 15.4882 5.7213  274.4934.64 16.703  5.30781 484.11 61.1  17.3062 5.11992  85.77 10.83 18.03774.91797 183.23 23.13 19.9018 4.46133 148.72 18.77 20.3543 4.36316 157.8519.92 21.0548 4.21606  86.99 10.98 21.9589 4.04782 136.42 17.22 22.88283.88644 218   27.51 24.6983 3.60472 418.6  52.83 26.7569 3.33188  87.6611.06 28.3461 3.14859  42.09  5.31 Characteristic peaks are indicated inbold.

AP1189 Nitrate Form X

The XRPD diffractogram for AP1189 nitrate salt Pattern 1 crystallisedfrom THF is shown in FIG. 21 . The corresponding XRPD diffractogram peaklist for nitrate salt Pattern 1 is shown in Table 16.

TABLE 16 XRPD diffractogram peak list for nitrate Pattern 1 from THF.Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%] 3.726 23.71408 179.91 19.17  7.5467 11.71468  136.08 14.5  11.8592 7.46261 408.46 43.5212.4917 7.08616 368.75 39.29 13.0853 6.76599 242.4  25.83 14.712 6.02134 295.86 31.53 15.2583 5.80697 522.07 55.63 16.9052 5.24478 238.5825.42 17.7422 4.99921 322.64 34.38 18.1478 4.88837 288.49 30.74 18.70344.74047 109.88 11.71 19.6432 4.51949 198.86 21.19 21.3874 4.15468 938.45100    22.9764 3.87083 226.32 24.12 24.1196 3.68989 348.22 37.11 25.10083.54782 430.13 45.83 26.6187 3.34886 432.7  46.11 27.7139 3.21896 372.3639.68 29.5135 3.02665 108.41 11.55 31.6588 2.82629 101.37 10.8 Characteristic peaks are indicated in bold.

AP1189 Cyclamate Form XI

The XRPD diffractogram for AP1189 cyclamate salt Pattern 2 crystallisedfrom THF is shown in FIG. 22 . The corresponding XRPD diffractogram peaklist for cyclamate salt Pattern 2 is shown in Table 17.

TABLE 17 XRPD diffractogram peak list for cyclamate Pattern 2 from THF.Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%]  3.1621 27.94165 179.59 22.76  5.2127 16.95363   87.48 11.09  7.0019 12.62477  789.01100    10.3525 8.5451  123.07 15.6  11.2896 7.83785 208.18 26.39 11.88117.44278  58.65  7.43 13.7568 6.4372  370.07 46.9  14.1759 6.24266  73.01 9.25 15.2643 5.8047  355.29 45.03 15.6888 5.64858 426.88 54.1  16.26585.44496 134.02 16.99 17.5752 5.04633 231.81 29.38 18.5197 4.78707  90.1311.42 19.1685 4.6303  187.78 23.8  20.0509 4.4285  273.46 34.66 20.70484.29009 321.46 40.74 21.4639 4.14005 317.94 40.3  21.7871 4.07598 242.1830.69 22.0945 4.01997 146.05 18.51 22.7092 3.91253 125.64 15.92 23.44033.79526 148.21 18.78 25.2406 3.52849 143   18.12 26.0048 3.42651 115.4314.63 27.7815 3.21128  54.76  6.94 Characteristic peaks are indicated inbold.

AP1189 Cyclamate Form XII

The XRPD diffractogram for AP1189 cyclamate salt Pattern 4 crystallisedfrom acetone is shown in FIG. 23 . The corresponding XRPD diffractogrampeak list for cyclamate salt Pattern 4 is shown in Table 18.

TABLE 18 XRPD diffractogram peak list for cyclamate Pattern 4 fromacetone. Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%]  6.290614.05077  102.71 26.16  7.3357 12.05109  335.85 85.54  9.3353 9.4659  8.68  2.21 11.3095 7.82408  86.03 21.91 12.7131 6.95747  47.33 12.0513.1319 6.74211  97.06 24.72 14.7863 5.98632 106.38 27.09 15.34355.77491 392.64 100    16.2948 5.43987 164.44 41.88 16.8716 5.25516128.27 32.67 17.8941 4.95711 338.3  86.16 19.0531 4.65811 184.82 47.0719.3468 4.58425  98.78 25.16 20.1366 4.40984 126.64 32.25 21.98464.04315 195.66 49.83 22.655  3.92501 157.07 40   24.0828 3.69238  90.6323.08 24.7776 3.59337  97.12 24.74 25.779  3.45315  28.08  7.15 27.10153.28757  6.68 1.7 29.0272 3.07624  38.61  9.83 Characteristic peaks areindicated in bold.

AP1189 Cyclamate Form XIII

The XRPD diffractogram for AP1189 cyclamate salt Pattern 5 crystallisedfrom THF is shown in FIG. 24 . The corresponding XRPD diffractogram peaklist for cyclamate salt Pattern 5 is shown in Table 19.

TABLE 19 XRPD diffractogram peak list for cyclamate Pattern 5 from THF.Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%]  3.3077 26.69018  8.98  0.58  5.5967 15.7911  187.14 12.03  6.4474 13.70936  956.81 61.52 7.1491 12.36521  828.98 53.3  7.588 11.65099   39.91  2.57 8.51710.38213  485.85 31.24  9.4338 9.36732 140.49  9.03  9.8762 8.95612582.21 37.44 10.2304 8.64685 266.94 17.16 10.4969 8.42791 570.75 36.7 10.9495 8.08048 182.36 11.73 11.6202 7.61559 281.21 18.08 11.88057.4431   57.72  3.71 12.3095 7.19065 168.44 10.83 13.0658 6.77606 629.6 40.48 13.3285 6.64308 706.95 45.46 13.7029 6.46239 245.66 15.8  14.11056.27663 180.03 11.58 14.6296 6.05509 1139.54  73.27 15.2647 5.804541555.19  100    16.2222 5.46402 565.52 36.36 16.6625 5.32062 949.9261.08 17.4798 5.06945 169.19 10.88 18.4631 4.80561 1460.84  93.9318.7365 4.73609 1201.35  77.25 19.8483 4.47324 1059.17  68.11 20.22984.38973 770.27 49.53 20.5681 4.3183  571.09 36.72 21.0659 4.21388−403.55   −25.95   21.1423 4.20229 606.37 38.99 21.346  4.1592  442.8428.47 21.6546 4.10402 389.75 25.06 22.0577 4.02991 385.89 24.81 22.58293.93737 598.47 38.48 22.8215 3.89352 314.13 20.2  23.6665 3.75949 387.3624.91 24.1076 3.69169 372.97 23.98 24.8773 3.5792  301.43 19.38 25.10013.54498 361.41 23.24 25.7105 3.46506 300.34 19.31 26.2315 3.39741 512.2432.94 26.9513 3.30828 549.96 35.36 27.7471 3.21519 196.84 12.66 28.68183.10992  34.66  2.23 29.4102 3.03453  16.29  1.05 29.9519 2.98088  42.78 2.75 30.844  2.89907  51.86  3.33 31.6221 2.82948  75.34  4.84 32.37062.76575  66.76  4.29 33.6225 2.66558  27.56  1.77 Characteristic peaksare indicated in bold.

AP1189 Besylate Form XIV

The XRPD diffractogram for AP1189 besylate salt Pattern 1 crystallisedfrom 2-Propanol:water 80:20% v/v is shown in FIG. 25 . The correspondingXRPD diffractogram peak list for besylate salt Pattern 1 is shown inTable 20.

TABLE 20 XRPD diffractogram peak list for besylate Pattern 1 from2-Propanol:water 80:20% v/v. Characteristic peaks are indicated in bold.Pos. [ °2θ ] d-spacing [ Å ] Height [ cts ] Rel. Int. [ % ] 3.217527.46024 62.4 1.8 8.3275 10.61794 225.23 6.49 9.0111 9.81393 198.54 5.729.9442 8.89498 282.36 8.14 10.7688 8.21566 502.34 14.48 11.2282 7.88052765.63 22.07 12.9603 6.83095 1879.15 54.16 13.1459 6.73493 2421.9 69.815.0755 5.87695 3469.81 100 15.9809 5.54599 542.33 15.63 16.4072 5.40284568.66 16.39 16.6812 5.31472 255.6 7.37 17.2775 5.13261 246.45 7.118.0701 4.90514 144.29 4.16 18.3074 4.84612 830.57 23.94 18.6991 4.74549548.41 15.81 18.9774 4.67651 338.15 9.75 19.4439 4.56536 154.45 4.4519.9239 4.45643 1750.81 50.46 20.252 4.38496 383.72 11.06 20.89394.24817 111.11 3.2 21.2688 4.17759 274.85 7.92 21.6759 4.10004 975.9328.13 22.0414 4.02953 110.44 3.18 22.7796 3.90382 519.42 14.97 23.12053.84703 470.89 13.57 23.5722 3.77431 700.52 20.19 24.8029 3.58976 481.6213.88 25.0701 3.54917 168.35 4.85 25.4203 3.50395 642.92 18.53 26.2683.39277 2290.5 66.01 26.4692 3.36743 1015.25 29.26 27.1415 3.28553372.17 10.73 28.1081 3.17471 152.82 4.4 28.5473 3.12686 199.35 5.7529.8458 2.99371 178.8 5.15 30.4198 2.93852 180.23 5.19 31.1212 2.87387102.11 2.94 32.0148 2.79567 64.16 1.85 33.1565 2.70197 130.3 3.7634.1106 2.62636 20.78 0.6

AP1189 Oxalate Form XV

The XRPD diffractogram for AP1189 oxalate salt Pattern 1 crystallisedfrom 2-Propanol:water 80:20% v/v is shown in FIG. 26 . The correspondingXRPD diffractogram peak list for oxalate salt Pattern 1 is shown inTable 21.

TABLE 21 XRPD diffractogram peak list for oxalate Pattern 1 from2-Propanol:water 80:20% v/v. Characteristic peaks are indicated in bold.Pos. [ °2θ ] d-spacing [ Å ] Height [ cts ] Rel. Int. [ % ] 7.246712.19886 450.79 12.92 10.7644 8.21907 1408.52 40.37 12.1117 7.30758459.79 13.18 13.8551 6.39177 2142.95 61.42 14.5121 6.10385 746.59 21.415.0495 5.88706 2731.17 78.28 15.6303 5.66959 1938.29 55.55 16.47775.37988 392.84 11.26 16.813 5.27334 908.28 26.03 17.3104 5.12291 635.7418.22 18.2079 4.87238 433.56 12.43 18.4636 4.80547 727.13 20.84 19.464.56161 3187.27 91.35 20.0756 4.42311 1393.22 39.93 21.6762 4.099981576.06 45.17 22.9254 3.87931 1254.01 35.94 23.2534 3.82534 3284.1 94.1323.789 3.74041 2446.77 70.13 24.2503 3.67029 918.98 26.34 24.76783.59477 612.09 17.54 25.8167 3.45105 3489.04 100 27.0213 3.29987 560.4416.06 27.9092 3.19688 158.4 4.54 28.5985 3.12137 374.56 10.74 29.29653.04605 218.5 6.26 29.7343 3.00468 369.86 10.6 30.1941 2.95996 331 9.4932.2394 2.7744 121.27 3.48 32.8731 2.72461 547.75 15.7

AP1189 Oxalate Form XVI

The XRPD diffractogram for AP189 oxalate salt Pattern 2 crystallisedfrom acetone is shown in FIG. 27 . The corresponding XRPD diffractogrampeak list for oxalate salt Pattern 2 is shown in Table 22.

TABLE 22 XRPD diffractogram peak list for oxalate Pattern 2 fromacetone. Characteristic peaks are indicated in bold. Pos. [ °2θ ]d-spacing [ Å ] Height [ cts ] Rel. Int. [ % ] 9.4812 9.32829 213.0710.76 11.2719 7.85012 650.76 32.86 12.1183 7.30367 220.43 11.13 13.09086.75757 112.09 5.66 13.9612 6.34341 478.29 24.15 15.2544 5.80845 324.4616.39 15.898 5.57471 1338.77 67.61 16.4116 5.4014 416.06 21.01 17.13595.1747 1606.29 81.12 17.9059 4.95387 1980.2 100 18.9149 4.69182 528.9926.71 19.5773 4.53453 1768.33 89.3 20.0364 4.43166 1097.18 55.41 21.21964.18715 1066.83 53.87 22.0167 4.03734 440.36 22.24 22.6679 3.92281185.33 59.86 23.0104 3.86518 733.85 37.06 23.3684 3.80677 872.51 44.0624.1748 3.68159 1377.48 69.56 24.3941 3.64898 1473.07 74.39 24.76363.59536 607.76 30.69 25.3618 3.51191 1006.2 50.81 25.7384 3.45851 366.8318.52 26.3029 3.38835 461.15 23.29 27.3315 3.26312 1359.3 68.64 28.433.13949 406.26 20.52 29.8952 2.98887 274.54 13.86 30.4479 2.93586 457.2223.09 31.2648 2.861 142.51 7.2 32.1862 2.78117 104.33 5.27 33.32372.68879 132.12 6.67 33.8688 2.64675 154.16 7.79 34.2555 2.61776 191.529.67 34.8614 2.5715 107.77 5.44

AP1189 Oxalate Form XVII

The XRPD diffractogram for AP1189 oxalate salt Pattern 4 crystallisedfrom THF is shown in FIG. 28 . The corresponding XRPD diffractogram peaklist for oxalate salt Pattern 4 is shown in Table 23.

TABLE 23 XRPD diffractogram peak list for oxalate Pattern 4 from THF.Characteristic peaks are indicated in bold. Pos. [ °2θ ] d-spacing [ Å ]Height [ cts ] Rel. Int. [ % ] 6.3181 13.98948 2384.52 98.7 8.173810.81722 70.4 2.91 10.5526 8.38352 2415.83 100 11.7369 7.54012 942.4139.01 12.3228 7.18288 950.21 39.33 12.5733 7.04032 282.57 11.7 12.8756.87604 519.84 21.52 13.2362 6.68366 89.53 3.71 14.0559 6.3009 588.2424.35 14.2029 6.23602 569.99 23.59 15.8039 5.6077 284.16 11.76 16.06695.51651 324.39 13.43 17.0726 5.19374 809.18 33.5 17.7878 4.98649 345.6414.31 18.4337 4.81321 1051.56 43.53 19.0388 4.65772 111.88 4.63 19.23044.61554 251.01 10.39 19.7672 4.4914 1361.5 56.36 20.2529 4.38479 312.6712.94 20.6597 4.29935 413.55 17.12 20.9554 4.23934 722.78 29.92 21.38234.15566 252.83 10.47 21.7977 4.07739 397.86 16.47 21.9785 4.04091 211.058.74 22.2699 3.992 329.34 13.63 22.6213 3.93077 878.11 36.35 23.23353.82856 349.11 14.45 23.517 3.78305 702.57 29.08 23.7795 3.74188 1071.6344.36 24.4105 3.64656 424.2 17.56 24.7951 3.58791 104.42 4.32 25.44263.50094 211.14 8.74 25.8594 3.44545 657.65 27.22 26.0571 3.41975 541.5222.42 26.5554 3.35393 72.07 2.98 27.1137 3.28884 147.15 6.09 27.52693.24041 139.31 5.77 27.8473 3.20119 46.04 1.91 28.3054 3.15302 258.7110.71 28.6747 3.11068 101.9 4.22 29.0198 3.07701 115.18 4.77 30.04422.97439 642.27 26.59 31.1015 2.87565 58.92 2.44 33.0328 2.7118 49.682.06 33.6771 2.66138 64.96 2.69 34.2549 2.61563 22.71 0.94

AP1189 (+)-Camphor-10-Sulfonic Acid Form XVIII

The XRPD diffractogram for AP1189 (+)-camphor-10-sulfonic acid saltPattern 1 crystallised from 2-Propanol:water 80:20% v/v is shown in FIG.29 . The corresponding XRPD diffractogram peak list for(+)-camphor-10-sulfonic acid salt Pattern 1 is shown in Table 24.

TABLE 24 XRPD diffractogram peak list for (+)-Camphor- 10-sulfonic acidPattern 1 from 2-Propanol:water 80:20% v/v. Characteristic peaks areindicated in bold. Pos. [ °2θ ] d-spacing [ Å ] Height [ cts ] Rel. Int.[ % ] 5.1412 17.18901 74.2 4.85 6.54 13.51547 654.67 42.8 7.665811.53287 63.53 4.15 9.3718 9.43695 250.57 16.38 9.8668 8.96463 153.8110.06 10.402 8.50455 214.98 14.05 10.9801 8.05138 117.55 7.69 11.52357.67925 673.45 44.03 12.2098 7.2431 124.1 8.11 12.9822 6.81949 581.0737.99 13.6946 6.46629 561.07 36.68 13.9583 6.34474 251.61 16.45 14.3456.16946 118.72 7.76 14.788 5.99059 1529.62 100 15.5959 5.67733 160.5410.5 15.8762 5.5777 338.29 22.12 16.1184 5.49898 574.21 37.54 17.21055.15243 315.7 20.64 18.131 4.89288 262.31 17.15 18.3504 4.83086 148.919.73 18.8333 4.71198 392.27 25.64 19.7635 4.49224 398.89 26.08 21.05974.21859 535.54 35.01 21.5101 4.13126 268.38 17.55 22.2216 3.99725 162.9910.66 22.7338 3.91158 214.89 14.05 23.1598 3.8374 165.06 10.79 23.83763.7329 280.8 18.36 25.0641 3.55295 203.63 13.31 25.6703 3.47039 163.3610.68 26.0558 3.41992 103.35 6.76 27.1796 3.28102 169.26 11.07 28.73623.10673 78.1 5.11 30.0563 2.97322 53.81 3.52 31.5327 2.8373 32.12 2.1

AP1189 Oxoglutarate Form XIX

The XRPD diffractogram for AP1189 oxoglutarate salt Pattern 1crystallised from acetone is shown in FIG. 30 . The corresponding XRPDdiffractogram peak list for oxoglutarate salt Pattern 1 is shown inTable 25.

TABLE 25 XRPD diffractogram peak list for oxoglutarate Pattern 1 fromacetone. Characteristic peaks are indicated in bold. Pos. [ °2θ ]d-spacing [ Å ] Height [ cts ] Rel. Int. [ % ] 9.1083 9.70943 477.9511.66 10.7459 8.23315 495.72 12.1 11.7595 7.51943 326.29 7.96 11.98887.38223 1205.72 29.42 12.8261 6.90214 1716.69 41.89 13.2196 6.69755 156738.24 13.3525 6.63121 2125.73 51.88 13.8276 6.39912 275.65 6.73 14.01386.31972 404.29 9.87 15.9327 5.56267 304.57 7.43 16.4363 5.39333 2897.870.72 16.8348 5.26657 4097.71 100 17.0851 5.18996 2766.55 67.51 17.93774.94515 772.63 18.86 18.2986 4.84842 340.41 8.31 19.4963 4.5532 718.7817.54 20.0696 4.42442 924.41 22.56 20.8084 4.26896 1505.3 36.74 21.60164.11397 3079.97 75.16 21.9908 4.04204 800.41 19.53 22.9225 3.87981615.58 15.02 23.4067 3.80062 3422.59 83.52 23.6024 3.76956 3716.86 90.7124.0809 3.69267 1988.14 48.52 24.1593 3.69001 1705.36 41.62 25.79463.4511 992.25 24.21 26.5255 3.35764 3336.34 81.42 26.9122 3.310263545.15 86.52 27.4146 3.25073 816.47 19.93 27.8612 3.19962 818.49 19.9728.8582 3.09132 551.01 13.45 29.9137 2.9846 238.13 5.81 30.337 2.94391890.96 21.74 30.8796 2.8934 536.6 13.1 32.2965 2.76963 570.06 13.9132.6262 2.74239 457.46 11.16 33.1486 2.70036 572.75 13.98 33.84022.64673 328.06 8.01 34.6933 2.58358 456.51 11.14

AP1189 DL-Mandelic Acid Form XX

The XRPD diffractogram for AP1189 DL-mandelic acid salt Pattern 2crystallised from methylethyl ketone is shown in FIG. 31 . Thecorresponding XRPD diffractogram peak list for DL-mandelic acid saltPattern 2 is shown in Table 26.

TABLE 26 XRPD diffractogram peak list for DL-mandelic acid Pattern 2from methylethyl ketone. Characteristic peaks are indicated in bold.Pos. [ °2θ ] d-spacing [ Å ] Height [ cts ] Rel. Int. [ % ] 5.327816.58759 1845 55.02 9.5789 9.23344 2024.97 60.39 9.968 8.87386 2381.6871.02 10.6699 8.28474 231.21 6.89 10.8512 8.15348 328.99 9.81 11.74477.53513 368.64 10.99 12.0395 7.35127 603.48 18.00 12.3648 7.158561003.51 29.92 13.3371 6.63884 1307.90 39.00 13.9345 6.35027 169.90 5.0714.7843 5.99208 2603.01 77.62 15.304 5.78972 241.37 7.2 16.0411 5.52532758.96 22.63 16.8321 5.26741 1019.62 30.41 17.0395 5.19944 178.31 5.3217.3113 5.12267 830.26 24.76 17.6081 5.03696 738.87 22.03 17.92464.94873 1940.47 57.87 18.5095 4.79366 874.43 26.08 19.1041 4.645782097.59 62.55 19.7677 4.49129 625.71 18.66 20.2411 4.3873 503.03 15.0020.6976 4.29157 616.33 18.38 21.2349 4.18417 1247.47 37.20 21.45354.14203 2057.15 61.34 21.8113 4.07152 163.21 4.87 22.8944 3.88451 381.1111.36 24.1665 3.68283 2677.35 79.84 24.5371 3.62805 739.38 22.05 24.79813.59044 1227.19 36.60 25.4748 3.49658 3353.42 100 26.3652 3.38048 266.487.95 26.885 3.31630 824.52 24.59 27.1313 3.28675 532.22 15.87 27.50183.24331 648.76 19.35 28.0542 3.18068 402.6 12.01 28.3699 3.14600 228.016.80 29.6695 3.01110 302.57 9.02 30.3377 2.94628 551.12 16.43 31.20692.86617 280.40 8.36 32.3828 2.76473 130.17 3.88 32.7924 2.73113 272.618.13 33.0937 2.70695 199.35 5.94 33.4812 2.67650 153.52 4.58 34.37392.60901 154.65 4.61 34.6967 2.58333 89.00 2.65

AP1189 DL-Mandelic Acid Form XXI

The XRPD diffractogram for AP1189 DL-mandelic acid salt Pattern 3crystallised from acetone is shown in FIG. 32 . The corresponding XRPDdiffractogram peak list for DL-mandelic acid salt Pattern 3 is shown inTable 27.

TABLE 27 XRPD diffractogram peak list for DL- mandelic acid Pattern 3from acetone. Characteristic peaks are indicated in bold. Pos. [ °2θ ]d-spacing [ Å ] Height [ cts ] Rel. Int. [ % ] 5.3893 16.39843 4912.2888.86 9.7591 9.06332 3991.44 72.2 10.0419 8.80866 5528.14 100 11.21987.88644 781.77 14.14 11.5373 7.66373 229.46 4.15 11.7936 7.504 1004.7918.18 12.6722 6.98565 1846.06 33.39 13.5326 6.54335 2579.7 46.66 14.35446.17052 699.64 12.66 15.0397 5.89088 1043.83 18.88 15.4731 5.726821523.04 27.55 15.6775 5.65264 1495.79 27.06 15.8208 5.59712 378.04 6.8416.5687 5.35053 3283.44 59.39 17.1736 5.16342 1270.64 22.98 18.11574.89697 3148.28 56.95 19.5677 4.53675 762.3 13.79 20.2232 4.39116 892.6216.15 20.6533 4.30067 1765.5 31.94 21.1402 4.20269 2967.73 53.68 21.71144.09342 2549.07 46.11 22.5571 3.94182 860.51 15.57 23.255 3.82508 1053.719.06 23.5888 3.77171 2097.93 37.95 24.5508 3.62604 5283.58 95.5825.3869 3.50849 2895.23 52.37 26.0622 3.41909 1624.06 29.38 27.03173.29589 972.29 17.59 27.2552 3.27209 1730.57 31.3 28.664 3.11439 405.067.33 28.9743 3.08174 371.42 6.72 29.8399 2.99429 436.53 7.9 30.40072.94032 770.85 13.94 30.6937 2.91051 239.34 4.33 31.1806 2.86854 293.275.31 32.8239 2.72858 186.18 3.37 33.4914 2.67571 336.08 6.08 33.96452.63951 205.17 3.71 34.5199 2.59831 222.06 4.02

AP1189 Hippuric Acid Form XXII

The XRPD diffractogram for AP1189 hippuric acid salt Pattern 1crystallised from methylethyl ketone is shown in FIG. 33 . Thecorresponding XRPD diffractogram peak list for hippuric acid saltPattern 1 is shown in Table 28.

TABLE 28 XRPD diffractogram peak list for hippuric acid Pattern 1 frommethylethyl ketone. Characteristic peaks are indicated in bold. Pos. [°2θ ] d-spacing [ Å ] Height [ cts ] Rel. Int. [ % ] 8.6143 10.25659113.08 8.83 9.598 9.21503 527.96 41.23 9.8144 9.00493 260.1 20.3110.8895 8.12492 928.65 72.51 11.4793 7.70874 893.63 69.78 11.75677.52125 410.35 32.04 12.6953 6.97294 640.66 50.03 13.255 6.67974 664.7651.91 13.8253 6.40018 374.81 29.27 14.1095 6.27188 395.92 30.92 14.42736.13954 822.58 64.23 14.8688 5.95818 960.42 74.99 15.5334 5.70474 717.0155.99 16.3714 5.4101 289.13 22.58 17.4516 5.08178 564.67 44.09 18.06214.91136 797.05 62.24 19.4664 4.55635 312.87 24.43 20.0768 4.422841099.31 85.84 20.686 4.29394 945.98 73.87 20.9823 4.23046 638.13 49.8321.989 4.04236 1034.88 80.81 22.3837 3.97197 1097 85.66 22.781 3.90358958.14 74.82 23.1141 3.84489 610.08 47.64 24.0708 3.69726 1280.66 10024.489 3.63506 1255.08 98.00 25.2989 3.5205 684.15 53.42 25.7814 3.45569537.56 41.98 27.1059 3.28976 557.88 43.56 28.072 3.17871 304.59 23.7829.1378 3.06482 381.24 29.77

AP1189 Formic Acid Form XXIII

The XRPD diffractogram for AP1189 formate salt Pattern 1 crystallisedfrom acetone is shown in FIG. 34 . The corresponding XRPD diffractogrampeak list for formate salt Pattern 1 is shown in Table 29.

TABLE 29 XRPD diffractogram peak list for formate Pattern 1 fromacetone. Characteristic peaks are indicated in bold. Pos. [ °2θ ]d-spacing [ Å ] Height [ cts ] Rel. Int. [ % ] 7.3974 11.95078 545.693.73 10.3677 8.53261 1240.38 8.47 10.6166 8.33313 1104.27 7.54 12.19327.25896 1192.4 8.14 13.2943 6.66011 12637.58 86.28 14.1263 6.269631121.3 7.66 15.0608 5.88266 14646.45 100 15.2423 5.81303 2665.72 18.216.7797 5.28372 2633.7 17.98 17.3341 5.11595 8220.13 56.12 17.99634.92918 2302.64 15.72 18.4846 4.80007 7429.09 50.72 18.7509 4.732487824.4 53.42 18.9261 4.68908 7877.5 53.78 19.1184 4.64235 4567.83 31.1920.5992 4.31184 5415.68 36.98 20.8504 4.26047 1014.98 6.93 21.35194.1615 596.99 4.08 21.845 4.06867 8642.95 59.01 22.3365 3.98024 835.565.7 22.5988 3.93464 2569.5 17.54 22.7594 3.90723 4206.51 28.72 23.13953.84391 843.2 5.76 23.6272 3.76566 8913.09 60.85 24.0258 3.70408 3919.6426.76 24.5257 3.6297 1772.27 12.1 24.8627 3.58126 2985.77 20.39 25.55623.48562 11808.59 80.62 26.7988 3.32676 1871.33 12.78 27.1478 3.284795298.04 36.17 27.555 3.23716 1232.48 8.41 28.1048 3.17508 688.88 4.728.5576 3.12575 1537.8 10.5 28.8538 3.09433 3072.99 20.98 29.22393.05598 2924.78 19.97 30.4606 2.93468 795.57 5.43 30.8589 2.8977 822.885.62 31.6975 2.82292 355.5 2.43 32.2437 2.77634 361.16 2.47 32.6762.74059 1050.97 7.18 33.0782 2.70818 1100.1 7.51 34.0175 2.63552 712.74.87

AP1189 DL-Lactic Acid Form XXIV

The XRPD diffractogram for AP1189 DL-lactic acid salt Pattern 1crystallised from acetone is shown in FIG. 35 . The corresponding XRPDdiffractogram peak list for L-lactic acid salt Pattern 1 is shown inTable 30.

TABLE 30 XRPD diffractogram peak list for L-lactic acid Pattern 1 fromacetone. Characteristic peaks are indicated in bold. Pos. [ °2θ ]d-spacing [ Å ] Height [ cts ] Rel. Int. [ % ] 3.8307 23.06604 3178.2447.86 7.6777 11.51498 1767.12 26.61 9.8772 8.95518 6641.34 100 11.91937.42511 4378.1 65.92 13.5622 6.52914 518.09 7.8 14.0188 6.31748 708.810.67 14.2103 6.2328 605.57 9.12 14.6766 6.03078 123.41 1.86 15.4095.75051 1357.73 20.44 15.7676 5.62053 469.6 7.07 18.0461 4.91568 554.638.35 18.2556 4.85976 852 12.83 18.6623 4.75475 897.72 13.52 19.28814.60186 483.92 7.29 19.8255 4.47833 386.24 5.82 20.1676 4.40313 1223.7418.43 20.4033 4.3528 919.15 13.84 20.6573 4.29984 1559.52 23.48 20.89054.25237 990.19 14.91 21.3526 4.16138 1157.33 17.43 21.646 4.10562 908.2313.68 22.3961 3.96979 855.37 12.88 22.6249 3.93017 939.37 14.14 22.9713.87172 2321.73 34.96 23.2857 3.82011 441.69 6.65 23.7043 3.75359 592.418.92 23.9203 3.72017 1448.41 21.81 25.3489 3.51366 1592.32 23.98 25.85163.44647 814.66 12.27 27.4586 3.24831 2881.16 43.38 27.8125 3.20777443.85 6.68 28.5067 3.13122 1135.06 17.09 28.663 3.1145 927.83 13.9729.5915 3.01635 53.45 0.8 29.9951 2.97668 37.42 0.56 30.429 2.93765222.79 3.35 31.4341 2.84598 106.84 1.61 31.8482 2.8099 177.22 2.6733.0644 2.70928 164.9 2.48 33.6444 2.66389 179.49 2.7

AP1189 DL-Lactic Acid Form XXV

The XRPD diffractogram for AP1189 DL-lactic acid salt Pattern 1crystallised from 2-propanol:water 80:20% v/v is shown in FIG. 36 . Thecorresponding XRPD diffractogram peak list for DL-lactic acid saltPattern 1 is shown in Table 31.

TABLE 31 XRPD diffractogram peak list for DL-lactic acid Pattern 1 from2-propanol:water 80:20% v/v. Characteristic peaks are indicated in bold.Pos. [ °2θ ] d-spacing [ Å ] Height [ cts ] Rel. Int. [ % ] 3.816223.15347 1804.22 34.05 7.6494 11.55762 1162.58 21.94 9.8321 8.99625298.36 100 11.8679 7.45715 3991.73 75.34 13.6586 6.48328 804.02 15.1714.1081 6.27769 790.27 14.92 14.2862 6.19986 766.33 14.46 15.33335.77875 955.8 18.04 15.8231 5.60095 461.73 8.71 18.161 4.88484 815.9615.4 18.5718 4.77771 802.78 15.15 19.2085 4.62076 490.09 9.25 19.75094.49507 401.86 7.58 20.5233 4.32761 965.62 18.22 20.9608 4.23826 1332.5625.15 21.282 4.17503 639.09 12.06 21.5473 4.12421 839.68 15.85 22.48983.95019 262.35 4.95 22.6827 3.92028 577.78 10.9 22.8882 3.88554 782.9814.78 23.2724 3.82226 1405.85 26.53 23.5751 3.77386 564.88 10.66 23.89543.72399 1240.54 23.41 25.0342 3.55417 184.12 3.48 25.5625 3.484791065.01 20.1 26.0731 3.41769 771.57 14.56 27.6295 3.2286 1820.33 34.3628.6694 3.11382 923.63 17.43 29.3516 3.04046 87.68 1.65 29.6094 3.0145879.61 1.5 29.8349 2.9923 57.71 1.09 30.216 2.95542 62.38 1.18 30.64162.91775 94.23 1.78 31.5599 2.83492 87.33 1.65 31.9945 2.79739 92.91 1.7534.1244 2.62751 173.05 3.27

AP1189 Glutaric Acid Form XXVI

The XRPD diffractogram for AP1189 glutaric acid salt Pattern 1crystallised from acetone is shown in FIG. 37 . The corresponding XRPDdiffractogram peak list for glutaric acid salt Pattern 1 is shown inTable 32.

TABLE 32 XRPD diffractogram peak list for glutaric acid Pattern 1 fromacetone. Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%]  3.218727.45066 1273.8 44.98  6.2662 14.10535 91.37 3.23  8.2746 10.685632609.46 92.15  8.6516 10.22081 1050.19 37.08  9.8059 9.02016 1139.1140.22 10.0791 8.76902 223.29 7.89 10.4696 8.44977 349.34 12.34 12.84616.89144 1821.76 64.33 13.6255 6.49895 355.14 12.54 14.3832 6.158231410.65 49.81 15.0994 5.86773 1435.45 50.69 15.8515 5.59098 2831.89 10016.2437 5.45684 1350.34 47.68 17.0593 5.19775 800.86 28.28 17.47165.07602 467.92 16.52 17.9619 4.93854 515.41 18.2 18.3427 4.83288 132.324.67 19.0191 4.66636 1161.13 41 19.7618 4.49262 942.09 33.27 20.16754.40316 327.58 11.57 20.5267 4.32691 479.36 16.93 21.0323 4.22402 514.6918.17 21.4391 4.14478 927.37 32.75 21.7032 4.09494 1737.14 61.34 21.94334.05068 2661.11 93.97 23.0149 3.86444 761.72 26.9 23.6232 3.76629 871.9130.79 24.1144 3.69067 335.65 11.85 24.5213 3.62734 178.61 6.31 24.99253.56296 523.88 18.5 26.0019 3.42689 608.37 21.48 26.47 3.36733 449.6415.88 27.108 3.28951 1957.29 69.12 27.6238 3.22926 659.12 23.28 28.17343.1675 497.17 17.56 28.8455 3.09521 1331.98 47.04 29.4794 3.03008 690.6924.39 30.5566 2.92567 279.74 9.88 31.4382 2.84561 247.41 8.74 32.34222.76811 174.16 6.15 33.8394 2.64898 126.9 4.48 Characteristic peaks areindicated in bold.

AP1189 Glutaric Acid Form XXVII

The XRPD diffractogram for AP1189 glutaric acid salt Pattern 2crystallised from methylethyl ketone is shown in FIG. 38 . Thecorresponding XRPD diffractogram peak list for glutaric acid saltPattern 2 is shown in Table 33.

TABLE 33 XRPD diffractogram peak list for glutaric acid Pattern 2 frommethylethyl ketone. Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%] 6.2713 14.09393 1348.45 21.68 10.0606 8.79234 2465.26 39.64 10.79648.19475 1055.44 16.97 12.5578 7.04898 1369.87 22.03 12.7174 6.96091816.87 13.14 13.4536 6.5816 976.38 15.7 14.0559 6.30088 4576.13 73.5814.3305 6.18077 2421.41 38.94 14.7434 6.00859 2331.2 37.48 15.11475.86181 3300.67 53.07 15.3445 5.77454 1725.44 27.74 15.6849 5.64529297.83 4.79 16.5052 5.37099 3574.38 57.47 16.7069 5.30659 2329.22 37.4516.9302 5.23709 3892.59 62.59 17.4284 5.08848 3107.29 49.96 18.00044.92807 1304.54 20.98 18.3123 4.84484 3268.21 52.55 18.6803 4.75021268.95 20.4 18.9049 4.6904 348.68 5.61 19.2764 4.60083 230.03 3.719.6067 4.52407 213.08 3.43 20.1361 4.4063 1951.43 31.38 20.2103 4.40121852.93 29.79 20.4529 4.33876 1029.79 16.56 20.9143 4.24407 525.31 8.4521.2592 4.17598 1295.43 20.83 21.6882 4.09434 6219.02 100 22.12294.01487 3700.13 59.5 22.5809 3.93447 3263.88 52.48 23.1992 3.83097666.23 10.71 23.9542 3.71192 738.95 11.88 24.3918 3.64631 1342.56 21.5924.9548 3.56529 4913.53 79.01 25.5599 3.48226 4269.78 68.66 25.99893.42444 1726.37 27.76 26.5216 3.35813 3601.16 57.91 26.8383 3.31921448.36 23.29 27.1448 3.28242 3733.35 60.03 27.6013 3.22916 1037 16.6728.1593 3.16643 3739.98 60.14 28.7121 3.10671 4338.65 69.76 28.97923.07869 1514.53 24.35 29.3573 3.03989 1131.3 18.19 29.7049 3.00511374.88 22.11 30.5161 2.92703 742.83 11.94 31.3096 2.85464 2126.37 34.1932.0253 2.79246 1658.17 26.66 32.9797 2.71379 391.9 6.3 34.0663 2.62968459.08 7.38 Characteristic peaks are indicated in bold.

AP1189 Glutaric Acid Form XXVIII

The XRPD diffractogram for AP1189 glutaric acid salt Pattern 4crystallised from acetone is shown in FIG. 91 The corresponding XRPDdiffractogram peak list for glutaric acid salt Pattern 4 is shown inTable 34.

TABLE 34 XRPD diffractogram peak list for glutaric acid Pattern 4 fromacetone. Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%]  6.264914.10824 2317.26 45.92  8.856 9.98546 1016.84 20.15 10.0581 8.794561068.48 21.17 10.3774 8.52465 827.42 16.4 10.7078 8.25549 282.03 5.5912.5708 7.04173 1531.07 30.34 13.4458 6.58542 495.2 9.81 13.8282 6.39883372.75 7.39 14.2416 6.21914 2854.8 56.57 15.238 5.81468 2052.8 40.6815.5797 5.6879 878.27 17.4 16.4839 5.37788 1494.63 29.62 16.8787 5.252965046.34 100 17.4128 5.09303 1366.17 27.07 18.1957 4.87561 1005.32 19.9219.1108 4.64417 1212.63 24.03 19.7816 4.48446 372.75 7.39 20.18934.39845 1158.28 22.95 20.6392 4.30358 1641.43 32.53 20.9102 4.248411980.44 39.25 21.6891 4.09756 1391.84 27.58 21.9308 4.05295 1854.7936.76 22.5489 3.94324 675.52 13.39 23.0328 3.86147 1238.92 24.55 23.59933.77005 740.75 14.68 23.8463 3.72846 584.45 11.58 24.536 3.6282 3003.7159.52 24.949 3.56907 820.3 16.26 25.2746 3.52382 778.83 15.43 26.08693.41591 1010.15 20.02 27.1988 3.27874 738.77 14.64 27.8279 3.20604 827.716.4 28.372 3.14577 1720.94 34.1 29.2659 3.04917 634.85 12.58 29.6313.01492 674.74 13.37 30.5003 2.93095 356.34 7.06 30.9655 2.88797 448.368.88 31.4367 2.84574 415.64 8.24 32.4495 2.7592 328.32 6.51 33.60522.66691 196.33 3.89 34.3331 2.61202 366.12 7.26 Characteristic peaks areindicated in bold.

AP1189 Adipic Acid Form XXIX

The XRPD diffractogram for AP1189 adipic acid salt Pattern 1crystallised from 2-Propanol:water 80:20% v/v is shown in FIG. 39 . Thecorresponding XRPD diffractogram peak list for adipic acid salt Pattern1 is shown in Table 35.

TABLE 35 XRPD diffractogram peak list for adipic acid Pattern 2 from2-Propanol:water 80:20 % v/v. Pos. [°2θ] d-spacing [Å] Height [cts] Rel.Int. [%]  5.2288 16.9012 374.38 14.26 10.4544 8.46204 332.6 12.6711.1721 7.92002 402.89 15.35 12.7447 6.94605 331.3 12.62 13.3934 6.611032624.96 100 14.5087 6.10526 2071.88 78.93 15.3038 5.78982 468.09 17.8315.7578 5.62399 302.36 11.52 17.0607 5.19734 820.45 31.26 17.6454 5.02641305.13 49.72 18.0415 4.91694 783.53 29.85 18.794 4.72173 270.99 10.3219.157 4.63306 977.8 37.25 20.5149 4.32579 76.13 2.9 21.0048 4.22949277.16 10.56 21.389 4.15438 746.25 28.43 22.3725 3.97063 121.59 4.6322.751 3.90866 583.38 22.22 22.996 3.86757 720.73 27.46 23.5265 3.781551287.83 49.06 23.9413 3.71696 408.65 15.57 24.4366 3.63972 198.1 7.5524.8265 3.58641 586.6 22.35 25.3953 3.50735 1334.01 50.82 25.52793.48943 1466.02 55.85 26.0524 3.42035 225.22 8.58 26.2942 3.38664 103.243.93 27.0894 3.29173 1235.27 47.06 27.4729 3.24665 840.7 32.03 28.06933.17637 83.67 3.19 28.9363 3.08315 67.85 2.58 29.4981 3.0282 169.21 6.4530.5878 2.92275 295.43 11.25 32.1777 2.78189 215.64 8.21 33.9424 2.6411887.52 3.33 34.5436 2.59658 170.22 6.48 Characteristic peaks areindicated in bold.

Conclusion

X-Ray Powder Diffraction Data was Collected for a Selection of DifferentAP1189 Salts.

Example 4: Thermogravimetric Analysis/Differential Scanning Calorimetryand Differential Scanning Calorimetry

Methods

For the TGA/DSC assessment, approximately, 5-10 mg of material was addedinto a pre-tared open aluminium pan, loaded into a TA InstrumentsDiscovery SDT 650 Auto-Simultaneous DSC and held at room temperature.The sample was then heated at a rate of 10° C./min from 30° C. to 400°C. during which time the change in sample weight was recorded along withthe heat flow response (DSC). Nitrogen was used as the sample purge gas,at a flow rate of 200 cm³/min.

For the DSC assessment, approximately, 1-5 mg of material was weighedinto an aluminium DSC pan and sealed non-hermetically with an aluminiumlid. The sample pan was then loaded into a TA Instruments Discovery DSC2500 differential scanning calorimeter equipped with a RC90 cooler. Thesample and reference were heated to 230° C. or 240° C. at a scan rate of10° C./min and the resulting heat flow response monitored. The samplewas re-cooled to 20° C. and then reheated again to 230° C. or 240° C.all at 10° C./min. Nitrogen was used as the purge gas, at a flow rate of50 cm³/min.

Results

Results from the TGA/DSC and DSC assessments are shown in Table 36.

TABLE 36 TGA/DSC (*) and DSC (**) data for AP1189 salts. Counter ionSolvent TGA/DSC or DSC results Acetic Acid Acetonitrile. Pattern 1Endothermic onset 192° C. (**) Acetic Acid Ethyl acetate, PatternEndothermic onset 1 + 2 172° C. (*) Note: Thermal data generated on2-MeTHF sample. Acetic Acid THF, Pattern 3 Endothermic onset 101° C. (*)p-Toluenesulfonic acid 2-propanol:water 90:10 Endothermic onset 234° C.(*) v/v/methanol, Pattern 1 Fumaric acid 2-propanol:water 90:10 v/v,Pattern 1 Endothermic onset 215° C. (*) Succinic acid 2-propanol:water90:10 v/v Endothermic onset 195° C. (*) Napadisylate pattern 12-propanol:water 90:10 % v/v 1^(st) onset 87° C. (*) 2^(nd) onset 187°C. (*) Esylate pattern 1 methylethyl ketone Onset 207° C. (*) Edisylatepattern 1 2-Propanol:water (80:20 % v/v) 1^(st) onset 78° C. (*) 2^(nd)onset 151° C. (*) Edisylate pattern 2 methylethyl ketone Onset 225° C.(*) Edisylate pattern 4 THF Onset 208 ° (*) Edisylate pattern 52-Propanol:water (80:20 % v/v) 1^(st) onset 59° C. (*) 2^(nd) onset 151°C. (*) Nitrate pattern 1 THF Onset 179° C. (*) Cyclamate pattern 2 THFOnset 130° C. (*) Cyclamate pattern 4 acetone Onset 138° C. (*)Cyclamate pattern 5 THF Onset 141° C. (*) Besylate pattern 12-Propanol:water 80:20 % v/v Onset 216° C. (*) Oxalate pattern 12-Propanol:water 80:20 % v/v Peak 211° C. (*) Oxalate pattern 2 acetoneOnset 207° C. (*) (+)-Camphor-10- 2-Propanol:water Onset 205° C. (*)sulfonic acid pattern 1 80:20 % v/v Oxoglutarate pattern 1 acetone Onset81° C. (*) DL-mandelic acid pattern 2 methylethyl ketone Onset 110° C.(*) Hippuric acid pattern 1 methylethyl ketone Onset 139° C. (*) Formicacid pattern 1 acetone Onset 169° C. (*) L-Lactic acid pattern 1 acetoneOnset 189° C. (*) DL-Lactic acid pattern 1 2-propanol:water 80:20 % v/vOnset 198° C. (*) Glutaric acid pattern 1 acetone 1^(st) onset 109° C.(*) 2^(nd) onset 160° C. (*) Glutaric acid pattern 2 methylethyl ketoneOnset 163° C. (*) Glutaric acid pattern 4 acetone 1^(st) onset 145° C.(*) 2^(nd) onset 160° C. (*) Adipic acid pattern 1 2-Propanol:water80:20 % v/v Onset 183° C. (*)

Example 5: Nuclear Magnetic Resonance

Methods

NMR experiments were performed on a Bruker AVIIIHD spectrometer equippedwith a DCH or PRODIGY cryoprobe operating at 500.12 or 500.23 MHz forprotons.

Experiments were performed in deuterated DMSO and each sample wasprepared to ca. 10 mM concentration.

Results

Chemical shifts and integration of ¹H-NMR signals from AP1189 salts aregiven in Table 37.

TABLE 37 Chemical shifts and integration of ¹H-NMR signals from AP1189salts. In DMSO-d₆. ¹H-NMR data AP1189 Salt Chemical shift (ppm)Integration Acetic Acid 8.16 1.00 7.89 1.04 7.78 1.05 7.63 2.04 6.991.00 6.65 1.07 6.48 1.20 6.30 1.72 6.21 2.31 4.04 0.28 3.64 0.40 3.571.32 1.98 0.30 1.84 2.98 1.26 0.54 1.17 0.18 0.87 0.09 p-Toluenesulfonic11.07 0.97 acid 8.16 1.00 7.92 1.08 7.82 1.08 7.74 1.09 7.66 1.11 7.492.32 7.37 3.26 7.15 3.29 6.80 1.05 6.59 1.11 6.34 2.04 2.28 3.18 2.040.16 1.87 0.05 1.27 0.77 0.85 0.11 Fumaric acid 13.34 1.42 8.17 1.007.90 1.37 7.80 1.18 7.73 1.14 7.65 1.23 7.08 0.92 6.76 0.90 6.52 0.916.46 1.73 6.41 0.94 6.33 0.92 2.09 0.17 1.90 0.01 1.24 0.16 Succinicacid 13.80 1.02 8.17 1.00 7.90 1.05 7.79 1.08 7.67 2.06 7.05 1.47 6.933.12 6.71 1.06 6.50 2.11 6.29 0.98 3.77 0.14 2.33 4.10 1.88 0.06 1.230.32 1.04 0.29 0.84 0.06

AP1189 napadisylate pattern 2:0.7543 (11.0629); 2.557 (8.8634); 1(8.1806); 2.6217 (7.941); 0.974 (7.9028); 1.0037 (7.7975); 0.8754(7.739); 1.0347 (7.656); 3.5752 (7.4103); 0.8399 (7.096); 0.7845(6.7841); 0.7859 (6.5499); 1.5389 (6.3551); 2.0976 (1.764).

AP1189 esylate pattern 1:1 (11.2407); 1.0302 (8.1724); 1.0864 (7.9088);1.1096 (7.7985); 1.0938 (7.7285); 1.1564 (7.6532); 3.1799 (7.5066);1.0215 (7.0896); 1.0396 (6.7843); 1.0711 (6.5428); 2.0916 (6.3686);2.2641 (2.4374); 3.2592 (1.0734).

AP1189 edisylate pattern 1:0.9389 (11.1051); 1 (8.1816); 1.1764 (7.915);1.2168 (7.8057); 1.0864 (7.7419); 1.1486 (7.66119); 4.2764 (7.4823);1.1528 (7.1064); 1.0797 (6.7887); 1.1652 (6.5561); 1.941 (6.3703);3.1838 (2.6499).

AP1189 edisylate pattern 2:1 (8.1754); 1.0457 (7.9043); 1.055 (7.7933);1.0496 (7.7126); 1.0385 (7.6399); 3.6468 (7.2657); 1.0648 (7.074);1.0135 (6.758); 1.0489 (6.5107); 2.0588 (6.3692); 1.8314 (2.6762);0.4358 (1.8961).

AP1189 edisylate pattern 4:0.9704 (11.1726); 0.3728 (8.6189); 1(8.1889); 1.0879 (7.9082); 1.1163 (7.8048); 1.1018 (7.7262); 1.2479(7.649); 3.9613 (7.4808); 1.239 (7.081); 1.0035 (6.7776); 0.9982(6.5529); 1.9363 (6.364); 5.8322 (2.7036); 0.3181 (1.9026); 2.3234(1.7578).

AP1189 edisylate pattern 5:1 (11.1488); 1.0198 (8.1751); 1.0482(7.9077); 1.0504 (7.7991); 1.0194 (7.7345); 1.0616 (7.6536); 3.4068(7.4789); 0.9855 (7.0894); 1.0035 (6.7829); 1.0279 (6.5554); 2.0024(6.3682); 2.1727 (2.6737).

AP1189 nitrate pattern 1:0.855 (11.0579); 1 (8.1758); 1.1992 (7.9089);1.1124 (7.8009); 1.1028 (7.7426); 1.1063 (7.6607); 3.1664 (7.4236);0.9762 (7.0947); 0.9159 (6.7819); 0.9574 (6.5523); 1.984 (6.3525);0.3361 (2.0666); 0.2449 (1.909); 0.3598 (0.9061).

AP1189 cyclamate pattern 2:0.8634 (11.3476); 1 (8.1712); 1.0915(7.9119); 1.0957 (7.7968); 1.0703 (7.7201); 1.1419 (7.6556); 3.5247(7.5221); 1.0013 (7.0879); 1.0173 (6.7856); 1.0326 (6.5094); 2.0216(6.3759); 1.0084 (2.8695); 0.0439 (2.0639); 2.0563 (1.889); 2.0597(1.599); 1.0453 (1.4747); 2.129 (1.157); 3.1001 (1.0312); 0.0716(0.9069).

AP1189 cyclamate pattern 4:0.9437 (11.3653); 1 (8.1707); 1.0501(7.9029); 1.0542 (7.7958); 1.0598 (7.7205); 1.0888 (7.6517); 3.4746(7.4706); 0.9954 (7.0905); 1.0072 (6.7896); 1.0321 (6.5128); 1.994(6.3726); 1.0213 (2.877); 0.7166 (1.909); 1.9717 (1.8707); 2.0065(1.5967); 0.9909 (1.4832); 2.0949 (1.1546); 3.0111 (1.037).

AP1189 besylate pattern 1:0.8981 (11.0474); 1 (8.1732); 1.0646 (7.9073);1.077 (7.8033); 1.0818 (7.7354); 1.0947 (7.6588); 2.0107 (7.5938);3.1874 (7.4508); 3.2895 (7.3107); 1.0376 (7.0824); 1.0335 (6.7775);1.0395 (6.5391); 2.042 (6.3614); 0.081 (1.9071); 0.1755 (1.0388).

AP1189 oxalate pattern 1:1 (8.1532); 1.0304 (7.8871); 1.0453 (7.7725);1.0065 (7.681); 1.0478 (7.6319); 2.9399 (7.1515); 1.1976 (7.0314);1.0234 (6.7175); 2.04 (6.4104); 1.014 (6.3244); 0.105 (1.0377).

AP1189 oxalate pattern 2:1 (8.1689); 1.0959 (7.902); 1.0853 (7.7878);1.2373 (7.7194); 1.4553 (7.6482); 2.6457 (7.5415); 0.988 (7.0686);1.0003 (6.7689); 2.0665 (6.4477); 0.9929 (6.3465); 0.063 (2.0968).

AP1189 oxalate pattern 4:1 (8.1515); 1.0445 (7.8892); 1.0462 (7.7742);1.0282 (7.6758); 1.0219 (7.6301); 2.6642 (7.1097); 1.2483 (7.024);1.0034 (6.7159); 2.0859 (6.3975); 0.997 (6.3192); 0.1217 (1.7624).

AP1189 (+)-camphor-10-sulfonic acid pattern 1:0.8814 (11.1521); 1(8.1744); 1.0627 (7.9089); 1.0996 (7.8055); 1.0638 (7.7356); 1.114(7.6573); 3.3236 (7.4351); 1.012 (7.0913); 1.0191 (6.7741); 1.0391(6.5267); 2.0264 (6.3743); 1.0414 (2.8818); 1.35 (2.661); 1.381(2.3787); 1.0478 (2.2319); 1.0068 (1.9412); 0.0876 (1.9105); 0.9801(1.8546); 1.1612 (1.7889); 2.1252 (1.276); 3.0996 (1.0314); 3.0831(0.7379).

AP1189 oxoglutarate pattern 1:1 (8.1669); 1.8014 (7.8993); 1.5121(7.7883); 1.1804 (7.7205); 1.0352 (7.6395); 0.9369 (7.0709); 0.9511(6.7756); 0.9802 (6.5257); 1.8945 (6.3703); 2.0183 (2.7771); 2.0935(2.3762); 3.775 (2.0831); 0.2799 (1.9065).

AP1189 DL-mandelic acid pattern 2:1 (8.1765); 1.1357 (7.9075); 1.1573(7.8014); 2.282 (7.658); 2.4615 (7.373); 2.4095 (7.2395); 1.2411(7.1718); 1.0362 (7.0527); 0.9926 (6.7419); 2.2546 (6.4249); 0.9906(6.3355); 1.1242 (4.6566); 1.9165 (2.4309); 2.6899 (2.0752); 2.7184(0.9137).

AP1189 DL-mandelic acid pattern 3:1 (8.1719); 1.0907 (7.8985); 1.1332(7.7964); 2.0988 (7.6516); 3.1244 (7.3791); 1.5978 (7.3108); 2.5396(7.2455); 1.2963 (7.173); 1.0635 (7.0434); 0.9514 (6.7353); 2.2616(6.418); 0.9986 (6.3312); 1.0491 (4.6436); 1.5842 (2.0853); 0.9834(1.8978); 0.3683 (0.9089).

AP1189 hippuric acid pattern 1:0.7548 (13.5715); 1.1969 (8.3963); 1(8.16); 1.0703 (7.8863); 2.3929 (7.8433); 1.087 (7.7812); 1.0158(7.6668); 1.0966 (7.633); 1.3863 (7.5276); 2.6135 (7.4589); 1.2686(7.0294); 1.028 (6.7102); 1.0111 (6.4352); 0.9644 (6.3695); 1.0492(6.3181); 2.4392 (3.7385); 0.3539 (2.0654); 0.4149 (1.8873); 0.3571(0.9132).

AP1189 formic acid pattern 1:1.0292 (8.2978); 1 (8.1572); 1.11 (7.8919);1.1402 (7.7789); 2.0493 (7.6393); 1.4368 (7.0232); 1.0484 (6.6976);1.0843 (6.4271); 0.8414 (6.3563); 1.3615 (6.315).

AP189 L-lactic acid pattern 1:1 (8.1477); 1.0199 (7.8914); 1.0281(7.7688); 1.016 (7.6355); 0.912 (7.5871); 0.8946 (6.9724); 0.9739(6.6292); 0.9826 (6.4603); 1.1694 (6.2913); 2.0197 (6.1996); 3.1739(1.8746).

AP1189 DL-lactic acid pattern 1:1 (8.162); 1.0734 (7.8983); 1.089(7.7857); 1.1388 (7.6686); 0.8544 (7.6311); 3.8862 (7.0181); 1.0121(6.703); 1.8676 (6.4245); 1.4225 (6.3346); 1.1312 (3.8217); 3.4204(1.1735).

AP1189 glutaric acid pattern 1:1 (8.1619); 1.2231 (7.8898); 1.2238(7.7746); 2.2688 (7.6176); 1.1544 (6.9851); 1.1233 (6.6576); 2.5919(6.4392); 2.628 (6.2658); 5.0598 (2.1953); 0.155 (2.0861); 2.5366(1.6883).

AP1189 glutaric acid pattern 2:1 (8.1501); 1.0837 (7.8878); 1.0944(7.7738); 2.0793 (7.6257); 1.07 (6.9923); 1.5227 (6.6621); 1.5132(6.44); 2.1718 (6.286); 4.2751 (2.1788); 0.1721 (1.8732); 2.132 (1.677);0.0775 (0.9072).

AP1189 glutaric acid pattern 4:1 (8.1477); 1.0427 (7.889); 1.0498(7.7725); 2.067 (7.6188); 1.0236 (6.9887); 1.0425 (6.6531); 4.4525(6.4277); 2.3299 (6.2728); 4.2147 (2.1823); 2.0993 (1.6841).

AP1189 adipic acid pattern 1:1 (8.1534); 1.0731 (7.889); 1.1078(7.7765); 2.1422 (7.6374); 1.3346 (7.0193); 1.1785 (6.6987); 1.078(6.4364); 2.1349 (6.3344); 0.3194 (3.7674); 6.2668 (2.1336); 1.1285(1.8523); 6.2972 (1.4746); 1.5977 (1.0395).

Conclusion

Chemical shift values and integration of peaks corresponds to theexpected salts.

Example 6: Solubility of AP1189 and its Salts

Methods

The solubility of AP1189 acetate (XRPD pattern 1), fumarate (XRPDpattern1), and succinate (XRDP pattern 1) salts were assessed in 0.5 Mbuffer solutions having pH of 1.2 and 4.5.

Results

The results of the study are shown in tables 38a and 38b for 0.5 M and0.2 M buffers, respectively. Table 38c shows the solubility of furtherAP1189 salts.

For the 0.5 M buffers, the highest solubility was observed for acetatePattern 1. Higher solubility was observed for succinate Pattern 1compared with fumarate Pattern 1. XRPD analysis showed acetate Pattern 1remained at pH 4.5. At pH 1.2 for the acetate, a likely HCl salt(assigned as HCl Pattern 1) was formed. Succinic acid was obtained fromthe succinate Pattern 1 experiment at pH 1.2. The free succinic acid inthe residual solids may indicate that the system was not saturated withrespect to the API and the solubility may be higher than that reported.

TABLE 38a Thermodynamic solubility results using 0.5 M buffers TestSolubility compound Buffer Initial pH 24 h pH (mM freebase) Acetate SaltpH 1.2 4.06 → 1.16 3.73 → 1.24 243.85 Pattern 1 (Form A) pH 4.5 4.604.60 1.05 Fumarate pH 1.2 1.46 → 1.19 1.23 7.84 Salt Pattern 1 pH 4.54.55 4.50 1.64 (Form D) Succinate pH 1.2 2.06 → 1.30 2.23 → 1.26 98.20Salt Pattern 1 pH 4.5 4.58 4.54 1.71 (Form B)

TABLE 38b Thermodynamic solubility results using 0.2 M buffers Test Saltor freebase input Solubility at 24 h compound Buffer Initial pH 24 h pHconcentration (mM) (mM freebase) Acetate pH 1.2 3.74 → 1.24 3.44 → 1.23210* 134.10 salt pH 4.5 4.52 4.54 74 2.23 pH 6.8 6.85 6.81 69 1.18Tosylate pH 1.2 1.22 1.26 31 0.31 Salt pH 4.5 4.91 → 4.45 4.47 34 0.17pH 6.8 6.77 6.87 30 —^(‡) Fumarate pH 1.2 1.35 → 1.18 1.29 38 10.90 SaltpH 4.5 4.47 4.48 39 2.73 pH 6.8 6.61 → 11.24 → 6.84 6.65 → 6.74 39 0.86Succinate pH 1.2 1.62 → 1.21 1.36 → 1.26  89* >36.26** Salt pH 4.5 4.484.56 36 4.26 pH 6.8 6.61 → 6.80 6.42 → 7.03 → 6.82 41 0.78 →: pHadjusted using hydrochloric acid or sodium hydroxide *: Estimated inputconcentration **: Fully soluble, input material was not sufficient tomaintain a slurry ^(‡): Not detected For pH 1.2 succinate experimentsthere was insufficient available material at the time of experiment tomaintain a suspension.

TABLE 38c Solubility of additional AP1189 salts Solubility HCl/KClBuffer 0.5 M pH Salt form AP1189 salt form 1.2 crystallised fromNapadisylate (Form III, IV) <15 mM 2-propanol:water 90:10 % v/v (FormIII) or THF (Form IV) Esylate (Form V) <15 mM methylethyl ketoneEdisylate (Form VII) <15 mM methylethyl ketone Nitrate (Form X) — THFCyclamate (Form XI, XII) <15 mM THF (Form XI) or acetone (Form XII)Besylate (Form XIV) ≥15 to <50 mM 2-Propanol:water 80:20 % v/v Oxalate(Form XV, XVI, XVII) <15 mM 2-Propanol:water 80:20 % v/v (Form XV) oracetone (Form XVI) or THF (Form XVII) (+)-Camphor-10-sulfonic acid <15mM 2-Propanol:water 80:20 % v/v (Form XVIII) Oxoglutarate (Form XIX) ≥15to <50 mM acetone DL-Mandelic acid (Form XX) ≥50 mM methylethyl ketoneHippuric acid (Form XXII) ≥50 mM methylethyl ketone Formic acid (FormXXIII) ≥15 to <50 mM acetone L-Lactic acid (Form XXIV) ≥50 mM acetoneDL-Lactic acid (Form XXV) ≥15 to <50 mM 2-propanol:water 80:20 % v/vGlutaric acid (Form XXVI) ≥15 to <50 mM acetone Adipic acid (Form XXIX)≥15 to <50 mM 2-Propanol:water 80:20 % v/v

Conclusion

The test compounds exhibited remarkably different solubilities,especially at low pH. Specifically, the acetate and succinate saltsshowed high solubility at pH 1.2, indicating the potential for usingthese compounds in applications where a high solubility at low pH isdesirable.

Example 7: Polymorph Study of AP1189 Succinate

Materials and Methods

Approximately 300 mg of the received succinate salt was added to 14 mLvials. The required volume of the appropriate solvent system was addedto each vial, and the experiments were stirred at 70-73° C. untilcomplete dissolution was achieved. The experiments were then cooled to68° C., and seeded with AP1189 succinate. 5 to 15% seed load was used.The experiments were stirred at 68° C. for another 1 h to allow forequilibration. The experiments were then cooled to 5° C. at 0.1° C./min,and stirred at 5° C. until isolation. The experiments (slurries) werevacuum filtered, and the cakes were each washed with 3 mL of therespective input solvent system (precooled at 5° C.). The solids wereanalysed by XRPD to check the polymorphic form. The remainder of thesolids were druid under vacuum at ambient for ca. 3 days. The driedsolids were characterised. The concentrations of the recovered motherliquors and was were determined by HPLC.

Results

Both damp and dried crystallised solids were consistent with Pattern 1of the succinate salt. Table 39 summarises the findings of the study.

TABLE 39 results from polymorph study for AP1189 succinate. Succ. Patt.1 is succinate Pattern 1. Yield (%) Purity (% area) XRPD Solvent systemIsolated HPLC Solid ML Damp Dried 1-Propanol:water 67.7 82.9 96.52 80.94Succ. Succ. 50:50 v/v % Patt. 1 Patt. 1 2-Propanol:water 71.3 84.7 96.2183.59 Succ. Succ. 50:50 v/v % Patt. 1 Patt. 1 Ethanol:water 65.9 74.396.22 88.75 Succ. Succ. 75:25 v/v % Patt. 1 Patt. 1 Ethanol:water 76.386.5 96.17 83.98 Succ. Succ. 50:50 v/v % Patt. 1 Patt. 1

Conclusion

AP1189 succinate exhibiting the crystal form of Pattern 1 was obtainedusing various crystallisation conditions.

Example 8: Polymorph Study of AP1189 Succinate

Materials and Methods

Approximately 300 mg of AP1189 was added to 20 mL vials. The requiredvolume of the appropriate solvent system was added to each vial, and theexperiments were stirred at 65-69° C. The experiments were then cooledto 55° C., and seeded with AP1189 succinate. 2% seed load was used. Theexperiments were stirred at 55° C. for another 1 h to allow forequilibration. The experiments were then cooled to 5° C. at 0.1° C./min,and stirred at 5° C. After ca. 18 h of stirring at 5° C., 200 μL aliquotof each slurry was extracted and centrifuged using 0.2 μm nylon tubes.The isolated solids were dried under vacuum at ambient and analysed byHPLC (purity). The concentration and purity of the mother liquors werealso determined by HPLC. To the remainder of the experiments,anti-solvent addition was carried out at 5° C., to reach the targetfinal ratio. Afterwards, stirring continued at 5° C. for another ca. 4h. The experiments (slurries) were vacuum filtered and the cakes eachwashed with 0.9 mL of the respective organic solvent (pre-cooled at 5°C.). The solids were dried under vacuum at ambient for ca. 48 h. Thedried solids were characterised. The mother liquors were subsampled andanalysed by HPLC for concentration and solution purity determination.The rest of the mother liquors were left open in an oven, to allow thesolvents to evaporate under vacuum, at ambient. After 3 days, theresidual solids were analysed by XRPD and HPLC (purity).

Results

All isolated solids were consistent with Pattern 1 of the succinatesalt. Table 40 summarises the findings of the study.

TABLE 40 results from polymorph study for AP1189 succinate. Succ. Patt.1 is succinate Pattern 1. PC is poorly crystalline. Yield (%) Solvent MLConc. Purity (% area) XRPD system Sample Isolated (mg/mL) HPLC Solid ML(Dried) 1- After — 10.91  88.0 95.64 83.03 — propanol:water cooling-only50:50 v/v % After 77.1 8.14 88.8 95.83 83.35 Succ. isolation Patt. 1 ML— — — 88.82 — Succ Evaporation Patt. 1, PC Ethanol:water After — 6.1590.3 95.69 82.42 — 50:50 v/v % cooling-only After 57.5 6.14 87.0 95.6779.73 Succ. isolation Patt. 1 ML — — — 91.20 — Succ. evaporation Patt.1, PC

Conclusion

AP1189 succinate exhibiting the crystal form of Pattern 1 was obtainedusing various crystallisation conditions. Isolated yield obtained wasbetween 65 and 80%. Addition of water as anti-solvent improved thetheoretical yield by 2 to 6% % w/w.

Example 9: Polymorph Study of AP1189 Succinate

Materials and Methods

Approximately 5 g of AP1189 succinate was added to temperaturecontrolled reactor in an EasyMax 102 (100 mL vessel). 55.6 mL (11.1vol.) of 1-propanol/water (50:50 v/v %) was added to the reactor, andthe experiment was stirred at 70° C. Target concentration was 90 mg/mL.Stirring speed was 200 rpm. When complete dissolution was observed, theexperiment was cooled to 55° C., and seeded with AP1189 succinate. 2%seed load was used, and it persisted with evidence of slurry formation.Post-seeding, stirring continued at 55° C. for 2 hours to allowexperiment to equilibrate. The experiment was cooled to 5° C. at 0.1°C./min, and allowed to stir at 5° C. for 1 h. Stirring speed wasincreased to 300 rpm during the cooling step. At 5° C., water (pH 7.22)was added to the experiment as an anti-solvent at 1 vol./hr, to reach atarget ratio of 40:60% v/v. 14 mL (2.8 vol.) of water was added.Post-addition, stirring continued at 5° C. for ca. 6 hours. A subsampleof the slurry was extracted into a 0.2 μm nylon tube and centrifuged.The concentration and solution purity of the isolated mother liquor weredetermined by HPLC. The isolated solid was dried under vacuum at ambientfor ca. 4 days, and analysed by HPLC for purity analysis. At 5° C., morewater was added as anti-solvent at 1 vol./hr, to reach a target ratio of30:70% v/v. 23.4 mL (4.6 vol.) of water was added. Stirring speed wasincreased further to 350 rpm during the addition. Post-addition,stirring continued at 5° C. for another 90 min. At 5° C., the slurry wasvacuum-filtered using Buchner funnel. The filter cake was washed with 10mL (2 vol.) of water (precooled to 5° C.) and dried under vacuum atambient for ca. 4 days. XRPD analysis was carried out on both the dampand dried solid sample. The dried solid was characterised. 10 mL aliquotof the mother liquor was left open in an oven to allow the solvent toevaporate under vacuum at ambient. The residual solid was analysed byXRPD and HPLC (purity). The concentration and solution purity of therest of the mother liquor and the wash were determined by HPLC.

Results

All samples were consistent with AP1189 succinate salt having XRPDPattern 1. The results are shown in Table 41.

TABLE 41 results from polymorph study for AP1189 succinate. Succ. Patt.1 is succinate Pattern 1. PC is poorly crystalline. Starting solventsystem: 1-propanol:water (50:50% v/v). Yield (%) ML conc. Purity (%area) XRPD Sample Isolated (mg/mL) HPLC Solid ML Wet Dry After ASA 1 —6.21 88.3 97.06 84.36 — Succ. (40:60 v/v) Patt 1. Final 80.9 3.37 92.496.56 84.86 Succ. Succ. sample Patt 1. Patt 1. Crust  6.4 — — 95.78 — —Succ. Patt 1. ML-Evap — — — 84.32 — — Succ. Patt 1.

Conclusion

AP1189 succinate exhibiting the crystal form of Pattern 1 was obtained.

Example 10: Polymorph Study of AP1189 Succinate

Materials and Methods

Approximately 10 g of the AP1189 succinate was added totemperature-controlled reactor in an EasyMax 402 (400 mL vessel). 100 mL(10 vol.) of 1-propanol:water (50:50 v/v %) was added to the reactor,and the experiment was stirred at 68° C. Concentration was 100 mg/mL.Stirring speed was 200 rpm. When complete dissolution was observed, theexperiment was polish-filtered at 70° C. to remove any insolubleimpurities, and the filtrate was added back into the reactor. 5 mL (0.5vol.) of 1-propanol:water (50:50 v/v %) was used to wash the reactor andpassed through the filter. 7 mL (0.7 vol.) of 1.propanol:water (50:50v/v %) was used to filter into the reactor. Concentration was 90 mg/mL.The experiment was allowed to equilibrate at 65° C., and then cooled to55° C. At 55° C., the experiment was seeded with 1% seed load, usingAP1189 succinate. Post-seeding, the experiment was allowed toequilibrate at 55° C. for ca. 1 hour. At 5° C., water was added to theexperiment as an anti-solvent at 1 vol./hr, to reach a target ratio of30:70% v/v. 74.7 mL (7.4 vol.) of water was added. Stirring speed wasincreased stepwise to 250 rpm during the addition. Post-addition,stirring continued at 5° C. for ca. 2.5 hours. At 5° C., the slurry wasvacuum filtered using Buchner funnel. The cake was washed with 10 mL (1vol.) of water (pre-cooled to 5° C.), and dried under vacuum at ambientfor 4 days. XRPD analysis was carried out on both the damp and driedsolid sample. The dried solid was characterised. 10 mL aliquot of themother liquor was left open in an oven to allow the solvent to evaporateunder vacuum at ambient. The residual solid was analysed by XRPD andHPLC (purity). The concentration and solution purity of the rest of themother liquor and the wash were determined by HPLC.

Results

All samples were consistent with AP1189 succinate salt having XRPDPattern 1. The results are shown in Table 42.

TABLE 42 results from polymorph study for AP1189 succinate. Succ. Patt.1 is succinate Pattern 1. PC is poorly crystalline. Starting solventsystem: 1-propanol:water (50:50% v/v). Yield (%) ML conc. Purity (%area) XRPD Sample Isolated (mg/mL) HPLC Solid ML Wet Dry Final 67.4 3.1993.3 96.51 82.39 Succ. Succ. sample Patt. 1 Patt. 1 Crust 20.1 — — 95.46— — Succ. Patt. 1 ML-Evap — — — 81.57 — — Succ. Patt. 1

Conclusion

AP1189 succinate exhibiting the crystal form of Pattern 1 was obtained.

Example 11: Further Solubility Study of AP1189 Acetate and AP1189Succinate

Materials and Methods

3.4 g of AP1189 succinate and 2.9 g of AP1189 acetate were added toseparate vials containing 10.0 mL of buffer solution pH 1.2 (onedetermination per salt). For the AP1189 acetate and AP1189 succinatesolutions, the pH was measured to 3.9 and 2.2 respectively. As a result,the pH was adjusted to 1.2 with concentrated hydrochloric acid in bothsolutions. Both sample preparations were diluted 500 times with thesample diluent (acetonitrile:water 1:1 v/v).

The diluted samples preparations were analysed by HPLC within 5 hoursfrom preparation and the content of AP1189 was determined from the areaunder the curve by comparing to standard solutions of AP1189 acetate andAP1189 succinate respectively.

Equilibrium solubilities were also assessed at pH 4.5 and pH 6.8following the procedure as described in WHO Technical Report Series1019, 2019 annex 4: Protocol to conduct equilibrium solubilityexperiments for the purpose of Biopharmaceutics ClassificationSystem-based classification of active pharmaceutical ingredients forbiowaiver.

Results

The sample materials in both vials were fully dissolved prior todilution.

The solubilities of the test compounds at pH 1.2 are shown in Table 43.The solubilities of the test compounds at pH 4.5 and pH 6.8 are shown inTable 44, where all purities were found to be within 92% and 95%.

TABLE 43 Determined concentration of AP1189 acetate and AP1189 succinatein pH 1.2 samples. The HPLC purities are also included in the table. Thefirst purity results are obtained from the CoAs for the lots and thesecond purity results were measured in the solubility experiment. SamplepH 1.2 (time) HPLC purity AP1189 acetate >617 mM (5 h) 99.3% →92.5% >223 mg/mL AP1189 succinate >593 mM (0.5 h) 99.4% → 91.9% >245mg/mL

TABLE 44 Summarized equilibrium solubilities (including standarddeviations) for AP1189 acetate and AP1189 succinate at 37° C. in bufferpH solutions 4.5 and 6.8. The HPLC purities are also included in thetable. The first purity results are obtained from the CoAs for the lotsand the second purity results were measured in the solubilityexperiment. Sample pH 4.5 (time) pH 6.8 (time) AP1189 acetate  3.2 mM ±0.0 mM (22 h)  2.4 mM ± 0.0 mM (22 h) 284 mg ± 3 mg/250 mL 216 mg ± 2mg/250 mL 99.3% → 91.9% 99.3% → 94.5% AP1189 succinate  3.6 mM ± 0.0 mM(22 h)  2.5 mM ± 0.1 mM (22 h) 370 mg ± 3 mg/250 mL  261 mg ± 13 mg/250mL 99.4% → 92.2% 99.4% → 93.7%

Example 12: Preparation of Further Polymorphs of AP1189 Salts

Tosylate Pattern 1

The tosylate salt of AP1189 having XRPD pattern 1 was prepared bycrystallisation from methanol.

Fumarate Pattern 1

The fumarate salt of AP1189 having XRPD pattern 1 was prepared bycrystallisation from isopropylalcohol:water 90:10 v/v.

Naphthalene-1,5-Disulfonic Acid Pattern 1

Naphthalene-1,5-Disulfonic Acid having XRPD Pattern 1 was prepared asfollows: 50 mg of AP1189 Acetate was weighed into a 1.5 mL HPLC vial anddissolved in 500 μL 2-Propanol:water 90:10% v/v. A further 500 μL2-Propanol:water 90:10% v/v was added to Naphthalene-1,5-disulfonic acid(1.1 molar equivalents), which was then transferred by pipette into theAPI. The resulting mixture was thermally cycled for 3 days between 40°C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at40° C. and 5° C.). Solids were isolated by centrifuge filtration andanalysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24hours then reanalysed by XRPD.

Naphthalene-1,5-Disulfonic Acid Pattern 2

Naphthalene-1,5-Disulfonic Acid having XRPD Pattern 2 was prepared asfollows: 50 mg of AP1189 Acetate was weighed into a 1.5 mL HPLC vial anddissolved in 500 μL THF. A further 500 μL of THF was added toNaphthalene-1,5-disulfonic acid (1.1 molar equivalents), which was thentransferred by pipette into the API. The resulting mixture was thermallycycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1° C./min withisothermal holds of 1 hour at 40° C. and 5° C.). Solids were isolated bycentrifuge filtration and analysed wet by XRPD. Sample was dried at 40°C. under vacuum for 24 hours then reanalysed by XRPD.

Ethanesulfonic Acid Pattern 1

Ethanesulfonic Acid having XRPD Pattern 1 was prepared as follows: 50 mgof AP1189 Acetate was weighed into a 1.5 mL HPLC vial and dissolved in 1mL of methylethyl ketone. Ethanesulfonic acid (1.1 molar equivalents)was transferred by pipette into the API. The resulting mixture wasthermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1°C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids wereisolated by centrifuge filtration and analysed wet by XRPD. Sample wasdried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.

Ethane-1,2-disulfonic Acid Pattern 1

Ethane-1,2-disulfonic Acid having XRPD Pattern 1 was prepared asfollows: 50 mg of AP1189 Acetate was weighed into a 1.5 mL HPLC vial anddissolved in 500 μL 2-Propanol:water (80:20% v/v). A further 500 μL of2-Propanol:water (80:20% v/v) was added to Ethane-1,2-disulfonic acid(1.1 molar equivalents), which was then transferred by pipette into theAPI. The resulting mixture was thermally cycled for 3 days between 40°C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at40° C. and 5° C.). Solids were isolated by centrifuge filtration andanalysed wet by XRPD giving Pattern 1. Sample was dried at 40° C. undervacuum for 24 hours then reanalysed by XRPD giving Pattern 5. Afterstorage at 40° C./75% RH for 24 hours the diffractogram was consistentwith pattern 1 by XRPD.

Ethane-1,2-disulfonic Acid Pattern 2

Ethane-1,2-disulfonic having XRPD Acid Pattern 2 was prepared asfollows: 50 mg of AP1189 Acetate was weighed into a 1.5 mL HPLC vial anddissolved in 500 μL methylethyl ketone. A further 500 μL of methylethylketone was added to Ethane-1,2-disulfonic acid (1.1 molar equivalents),which was then transferred by pipette into the API. The resultingmixture was thermally cycled for 3 days between 40° C. and 5° C. (Ramprate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and 5° C.).Solids were isolated by centrifuge filtration and analysed wet by XRPD.Sample was dried at 40° C. under vacuum for 24 hours then reanalysed byXRPD.

Ethane-1,2-disulfonic Acid Pattern 4

Ethane-1,2-disulfonic Acid having XRPD Pattern 4 was prepared asfollows: 50 mg of AP1189 Acetate was weighed into a 1.5 mL HPLC vial anddissolved in 500 μL THF. A further 500 μL of THF was added toEthane-1,2-disulfonic acid (1.1 molar equivalents), which was thentransferred by pipette into the API. The resulting mixture was thermallycycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1° C./min withisothermal holds of 1 hour at 40° C. and 5° C.). Solids were isolated bycentrifuge filtration and analysed wet by XRPD. Sample was dried at 40°C. under vacuum for 24 hours then reanalysed by XRPD.

Ethane-1,2-disulfonic Acid Pattern 5

Ethane-1,2-disulfonic Acid having XRPD Pattern 5 was prepared asfollows: 50 mg of AP1189 Acetate was weighed into a 1.5 mL HPLC vial anddissolved in 500 μL 2-Propanol:water (80:20% v/v). A further 500 μL of2-Propanol:water (80:20% v/v) was added to Ethane-1,2-disulfonic acid(1.1 molar equivalents), which was then transferred by pipette into theAPI. The resulting mixture was thermally cycled for 3 days between 40°C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at40° C. and 5° C.). Solids were isolated by centrifuge filtration andanalysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24hours then reanalysed by XRPD.

Nitric Acid Pattern 1

Nitric Acid having XRPD Pattern 1 was prepared as follows: 50 mg ofAP1189 Acetate was weighed into a 1.5 mL HPLC vial and dissolved in 1 mLof THF. Nitric acid (1.1 molar equivalents) was transferred by pipetteinto the API. The resulting mixture was thermally cycled for 3 daysbetween 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holdsof 1 hour at 40° C. and 5° C.). Solids were isolated by centrifugefiltration and analysed wet by XRPD. Sample was dried at 40° C. undervacuum for 24 hours then reanalysed by XRPD.

Cyclamic Acid Pattern 2

Cyclamic Acid having XRPD Pattern 2 was prepared as follows: 50 mg ofAP1189 Acetate was weighed into a 1.5 mL HPLC vial and dissolved in 500μL THF. A further 500 μL of THF was added to Cyclamic acid (1.1 molarequivalents), which was then transferred by pipette into the API. Theresulting mixture was thermally cycled for 3 days between 40° C. and 5°C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and5° C.). Solids were isolated by centrifuge filtration and analysed wetby XRPD. Sample was dried at 40° C. under vacuum for 24 hours thenreanalysed by XRPD.

Cyclamic Acid Pattern 4

Cyclamic Acid having XRPD Pattern 4 was prepared as follows:

50 mg of AP1189 Acetate was weighed into a 1.5 mL HPLC vial anddissolved in 500 μL Acetone. A further 500 μL of Acetone was added toCyclamic acid (1.1 molar equivalents), which was then transferred bypipette into the API. The resulting mixture was thermally cycled for 3days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermalholds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifugefiltration and analysed wet by XRPD. Sample was dried at 40° C. undervacuum for 24 hours then reanalysed by XRPD.

Cyclamic Acid Pattern 5

Cyclamic Acid having XRPD Pattern 5 was prepared as follows: 50 mg ofAP1189 Acetate was weighed into a 1.5 mL HPLC vial and dissolved in 500μL THF. A further 500 μL of THF was added to Ethane-1,2-disulfonic acid(1.1 molar equivalents), which was then transferred by pipette into theAPI. The resulting mixture was thermally cycled for 3 days between 40°C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at40° C. and 5° C.). Solids were isolated by centrifuge filtration andanalysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24hours then reanalysed by XRPD. After storage at 40° C./75% RH for 24hours the diffractogram was consistent with pattern 5 by XRPD.

Benzenesulfonic Acid Pattern 1

Benzenesulfonic Acid having XRPD Pattern 1 was prepared as follows: 50mg of AP1189 Acetate was weighed into a 1.5 mL HPLC vial and dissolvedin 1 mL of 2-Propanol:water 80:20% v/v. Benzenesulfonic acid (1.1 molarequivalents) was transferred by pipette into the API. The resultingmixture was thermally cycled for 3 days between 40° C. and 5° C. (Ramprate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and 5° C.).Solids were isolated by centrifuge filtration and analysed wet by XRPD.Sample was dried at 40° C. under vacuum for 24 hours then reanalysed byXRPD.

Oxalic Acid Pattern 1

Oxalic Acid having XRPD Pattern 1 was prepared as follows: 50 mg ofAP1189 Acetate was weighed into a 1.5 mL HPLC vial and dissolved in 500μL 2-Propanol:water 80:20% v/v. A further 500 μL of 2-Propanol:water80:20% v/v was added to Oxalic acid (1.1 molar equivalents), which wasthen transferred by pipette into the API. The resulting mixture wasthermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1°C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids wereisolated by centrifuge filtration and analysed wet by XRPD. Sample wasdried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.

Oxalic Acid Pattern 2

Oxalic Acid having XRPD Pattern 2 was prepared as follows:

50 mg of AP1189 Acetate was weighed into a 1.5 mL HPLC vial anddissolved in 500 μL Acetone. A further 500 μL of Acetone was added toOxalic acid (1.1 molar equivalents), which was then transferred bypipette into the API. The resulting mixture was thermally cycled for 3days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermalholds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifugefiltration and analysed wet by XRPD. Sample was dried at 40° C. undervacuum for 24 hours then reanalysed by XRPD.

Oxalic Acid Pattern 4

Oxalic Acid having XRPD Pattern 4 was prepared as follows:

50 mg of AP1189 Acetate was weighed into a 1.5 mL HPLC vial anddissolved in 500 μL THF. A further 500 μL of THF was added to Oxalicacid (1.1 molar equivalents), which was then transferred by pipette intothe API. The resulting mixture was thermally cycled for 3 days between40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hourat 40° C. and 5° C.). Solids were isolated by centrifuge filtration andanalysed wet by XRPD. Sample was dried at 40° C. under vacuum for 24hours then reanalysed by XRPD.

(+)-Camphor-10-Sulfonic Acid Pattern 1

(+)-Camphor-10-Sulfonic Acid having XRPD Pattern 1 was prepared asfollows:

50 mg of AP1189 Acetate was weighed into a 1.5 mL HPLC vial anddissolved in 1 mL of 2-Propanol:water 80:20% v/v.(+)-camphor-10-sulfonic acid (1.1 molar equivalents) was transferred bypipette into the API. The resulting mixture was thermally cycled for 3days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermalholds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifugefiltration and analysed wet by XRPD. Sample was dried at 40° C. undervacuum for 24 hours then reanalysed by XRPD.

Ketoglutaric Acid Pattern 1

Ketoglutaric Acid having XRPD Pattern 1 was prepared as follows:

50 mg of AP1189 Acetate was weighed into a 1.5 mL HPLC vial anddissolved in 1 mL of Acetone. Ketoglutaric acid (1.1 molar equivalents)was transferred by pipette into the API. The resulting mixture wasthermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1°C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids wereisolated by centrifuge filtration and analysed wet by XRPD. Sample wasdried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.

DL-Mandelic Acid Pattern 2

DL-Mandelic Acid having XRPD Pattern 2 was prepared as follows:

50 mg of AP1189 Acetate was weighed into a 1.5 mL HPLC vial anddissolved in 500 μL methylethyl ketone. A further 500 μL of methylethylketone was added to DL-Mandelic acid (1.1 molar equivalents), which wasthen transferred by pipette into the API. The resulting mixture wasthermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1°C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids wereisolated by centrifuge filtration and analysed wet by XRPD. Sample wasdried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.

DL-Mandelic Acid Pattern 3

DL-Mandelic Acid having XRPD Pattern 3 was prepared as follows:

50 mg of AP1189 Acetate was weighed into a 1.5 mL HPLC vial anddissolved in 500 μL Acetone. A further 500 μL of Acetone was added toDL-Mandelic acid (1.1 molar equivalents), which was then transferred bypipette into the API. The resulting mixture was thermally cycled for 3days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermalholds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifugefiltration and analysed wet by XRPD. Sample was dried at 40° C. undervacuum for 24 hours then reanalysed by XRPD.

Hippuric Acid Pattern 1

Hippuric Acid having XRPD Pattern 1 was prepared as follows:

50 mg of AP1189 Acetate was weighed into a 1.5 mL HPLC vial anddissolved in 500 μL methylethyl ketone. A further 500 μL of methylethylketone was added to Hippuric acid (1.1 molar equivalents), which wasthen transferred by pipette into the API. The resulting mixture wasthermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1°C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids wereisolated by centrifuge filtration and analysed wet by XRPD. Sample wasdried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.

Formic Acid Pattern 1

Formic Acid having XRPD Pattern 1 was prepared as follows: 50 mg ofAP1189 Acetate was weighed into a 1.5 mL HPLC vial and dissolved in 1 mLof Acetone. Formic acid (1.1 molar equivalents) was transferred bypipette into the API. The resulting mixture was thermally cycled for 3days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermalholds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifugefiltration and analysed wet by XRPD. Sample was dried at 40° C. undervacuum for 24 hours then reanalysed by XRPD.

L-Lactic Acid Pattern 1

L-Lactic Acid having XRPD Pattern 1 was prepared as follows:

50 mg of AP1189 Acetate was weighed into a 1.5 mL HPLC vial anddissolved in 500 μL Acetone. A further 500 μL of Acetone was added toL-Lactic acid (1.1 molar equivalents), which was then transferred bypipette into the API. The resulting mixture was thermally cycled for 3days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermalholds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifugefiltration and analysed wet by XRPD. Sample was dried at 40° C. undervacuum for 24 hours then reanalysed by XRPD.

DL-Lactic Acid Pattern 1

DL-Lactic Acid having XRPD Pattern 1 was prepared as follows:

50 mg of AP1189 Acetate was weighed into a 1.5 mL HPLC vial anddissolved in 500 μL 2-propanol:water 80:20% v/v. A further 500 μL of2-propanol:water 80:20% v/v was added to DL-Lactic acid (1.1 molarequivalents), which was then transferred by pipette into the API. Theresulting mixture was thermally cycled for 3 days between 40° C. and 5°C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and5° C.). Solids were isolated by centrifuge filtration and analysed wetby XRPD. Sample was dried at 40° C. under vacuum for 24 hours thenreanalysed by XRPD.

Glutaric Acid Pattern 1

Glutaric Acid having XRPD Pattern 1 was prepared as follows:

50 mg of AP1189 Acetate was weighed into a 1.5 mL HPLC vial anddissolved in 500 μL Acetone. A further 500 μL of Acetone was added toGlutaric acid (1.1 molar equivalents), which was then transferred bypipette into the API. The resulting mixture was thermally cycled for 3days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermalholds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifugefiltration and analysed wet by XRPD. Sample was dried at 40° C. undervacuum for 24 hours then reanalysed by XRPD.

Glutaric Acid Pattern 2

Glutaric Acid having XRPD Pattern 2 was prepared as follows:

50 mg of AP1189 Acetate was weighed into a 1.5 mL HPLC vial anddissolved in 500 μL methylethyl ketone. A further 500 μL of methylethylketone was added to Glutaric acid (1.1 molar equivalents), which wasthen transferred by pipette into the API. The resulting mixture wasthermally cycled for 3 days between 40° C. and 5° C. (Ramp rate: 0.1°C./min with isothermal holds of 1 hour at 40° C. and 5° C.). Solids wereisolated by centrifuge filtration and analysed wet by XRPD. Sample wasdried at 40° C. under vacuum for 24 hours then reanalysed by XRPD.

Glutaric Acid Pattern 4

50 mg of AP1189 Acetate was weighed into a 1.5 mL HPLC vial anddissolved in 500 μL Acetone. A further 500 μL of Acetone was added toGlutaric acid (1.1 molar equivalents), which was then transferred bypipette into the API. The resulting mixture was thermally cycled for 3days between 40° C. and 5° C. (Ramp rate: 0.1° C./min with isothermalholds of 1 hour at 40° C. and 5° C.). Solids were isolated by centrifugefiltration and analysed wet by XRPD. Sample was dried at 40° C. undervacuum for 24 hours then reanalysed by XRPD giving Pattern 1. Storage ofPattern 1 at 40° C./75% RH for 24 hours resulted in a new pattern byXRPD (Pattern 4)

Adipic Acid Pattern 1

Adipic Acid having XRPD Pattern 1 was prepared as follows:

50 mg of AP1189 Acetate was weighed into a 1.5 mL HPLC vial anddissolved in 500 μL 2-Propanol:water 80:20% v/v. A further 500 μL of2-Propanol:water 80:20% v/v was added to Adipic acid (1.1 molarequivalents), which was then transferred by pipette into the API. Theresulting mixture was thermally cycled for 3 days between 40° C. and 5°C. (Ramp rate: 0.1° C./min with isothermal holds of 1 hour at 40° C. and5° C.). Solids were isolated by centrifuge filtration and analysed wetby XRPD. Sample was dried at 40° C. under vacuum for 24 hours thenreanalysed by XRPD.

Example 13: FT-IR Measurements

Materials and Methods

Infrared spectroscopy was carried out on a Bruker ALPHA P spectrometer.Sufficient material was placed onto the centre of the plate of thespectrometer and the spectra were obtained using the followingparameters: Resolution: 4 cm⁻¹; Background Scan Time: 16 scans; SampleScan Time: 16 scans; Data Collection: 4000 to 400 cm⁻¹, Result Spectrum:Transmittance; Software: OPUS version 6.

Results

Tables 45-68 show the FT-IR peak lists for various AP1189 saltpolymorphs.

FIG. 92 shows the IR spectrum of AP1189 acetate Pattern 1.

TABLE 45 FT-IR peak list for AP1189 napadisylate Pattern 1 AbsoluteRelative Wavenumber Intensity Intensity 3466.6868 0.886 0.028 3348.60670.877 0.078 3191.3211 0.895 0.005 3151.5669 0.898 0.001 3118.6795 0.90.002 3043.0897 0.901 0.006 2968.754 0.91 0.007 2872.5429 0.92 0.0031675.6159 0.787 0.084 1632.1472 0.684 0.245 1531.9778 0.681 0.2691494.9203 0.83 0.074 1440.297 0.795 0.138 1347.2845 0.725 0.209 1295.4350.881 0.05 1237.4246 0.815 0.084 1217.2817 0.79 0.064 1193.3462 0.7470.08 1166.4915 0.664 0.26 1081.1736 0.832 0.063 1025.0437 0.574 0.3731025.0437 0.574 0.373  968.7163 0.7 0.182  890.1769 0.892 0.035 870.6032 0.916 0.008  855.9669 0.849 0.085  839.5018 0.918 0.012 793.4597 0.734 0.182  776.4759 0.797 0.047  758.5855 0.743 0.113 721.6015 0.622 0.243  661.4094 0.796 0.022  644.2371 0.781 0.024 644.2371 0.781 0.024  599.9555 0.586 0.086  558.3191 0.596 0.048 518.543 0.562 0.118  518.543 0.562 0.182  463.4629 0.572 0.096 463.4629 0.572 0.115  441.8127 0.655 0.02

TABLE 46 FT-IR peak list for AP1189 napadisylate Pattern 2 AbsoluteRelative Wavenumber Intensity Intensity 3457.0059 0.915 0.001 3330.97170.895 0.001 3121.7024 0.877 0.003 1676.3847 0.833 0.053 1624.8494 0.7890.109 1606.2505 0.811 0.009 1579.1694 0.836 0.017 1527.463 0.779 0.1421493.3067 0.835 0.034 1444.2738 0.846 0.036 1414.9494 0.881 0.0051395.9339 0.875 0.018 1348.1145 0.836 0.062 1297.3292 0.888 0.011237.2278 0.839 0.019 1189.0537 0.713 0.019 1155.8105 0.703 0.1431029.7055 0.641 0.249  969.3187 0.744 0.036  888.0521 0.823 0.022 850.9679 0.824 0.037  790.0213 0.729 0.102  765.1716 0.725 0.122 720.6873 0.77 0.013  700.4846 0.759 0.033  662.5114 0.753 0.034 601.4669 0.575 0.152  601.4669 0.575 0.152  564.0144 0.639 0.029 525.7536 0.621 0.051  491.9536 0.652 0.005  462.2125 0.621 0.049

TABLE 47 FT-IR peak list for AP1189 esylate Pattern 1. Absolute RelativeWavenumber Intensity Intensity 3349.7247 0.955 0.001 3277.377 0.9570.005 3187.823 0.947 0.001 3141.9143 0.934 0.06 3017.314 0.958 0.0072935.0847 0.962 0.009 2879.2134 0.971 0.001 1684.2122 0.907 0.0461656.4218 0.942 0.006 1627.0362 0.864 0.117 1612.4111 0.888 0.0161526.9552 0.886 0.091 1494.7631 0.919 0.04 1459.0201 0.908 0.0571446.057 0.924 0.017 1416.6283 0.964 0.007 1360.4768 0.918 0.0551335.6655 0.926 0.033 1297.1634 0.948 0.021 1240.7436 0.939 0.0271189.9984 0.855 0.112 1150.3317 0.869 0.044 1134.1169 0.873 0.0091103.8023 0.909 0.016 1036.5662 0.826 0.155 1010.6467 0.936 0.008982.056 0.898 0.059 982.056 0.898 0.059 982.056 0.898 0.059 982.0560.898 0.059 887.7475 0.939 0.039 849.2158 0.95 0.028 783.8148 0.9240.032 745.9402 0.869 0.104 745.9402 0.869 0.104 699.2813 0.877 0.066651.1217 0.883 0.017 629.68 0.884 0.013 604.5022 0.88 0.036 577.54110.88 0.028 530.9237 0.871 0.084 490.6684 0.926 0.008 471.9556 0.8880.055 471.9556 0.888 0.055 455.469 0.913 0.016 406.1926 0.94 0.007

TABLE 48 FT-IR peak list for AP1189 edisylate Pattern 2. AbsoluteRelative Wavenumber Intensity Intensity 3462.9446 0.995 0.001 3257.08050.991 0.002 3150.1577 0.99 0.012 2884.3168 0.998 0 2866.5313 0.997 02866.5313 0.997 0 2826.2672 0.995 0.005 2242.0076 0.994 0.006 2159.63690.994 0.007 2135.3353 0.994 0.008 2035.2014 0.993 0.011 1985.1016 0.9950.009 1926.5194 0.996 0.001 1901.158 0.996 0.002 1841.97 0.997 0.0021816.3004 0.998 0.001 1808.22 0.998 0 1777.6607 0.997 0.002 1734.31360.997 0.002 1684.9728 0.984 0.009 1655.6732 0.989 0.003 1625.4399 0.9740.026 1625.4399 0.974 0.026 1615.0231 0.98 0.001 1527.2346 0.982 0.0141496.9895 0.991 0.004 1442.4714 0.989 0.008 1356.9431 0.989 0.0081297.8821 0.995 0.002 1229.6559 0.981 0.008 1207.4986 0.981 0.0071176.4347 0.981 0.016 1139.4076 0.988 0.003 1106.709 0.992 0.0011065.3893 0.995 0.001 1027.718 0.973 0.026 1027.718 0.973 0.026 983.24160.986 0.009 983.2416 0.986 0.009 958.9998 0.994 0.002 958.9998 0.9940.002 916.0674 0.996 0.001 898.6396 0.997 0 864.6502 0.996 0.001850.6436 0.994 0.004 813.3872 0.995 0.001 790.6623 0.991 0.004 766.29610.988 0.007 731.909 0.983 0.013 702.5531 0.992 0.003

TABLE 49 FT-IR peak list for AP1189 edisylate Pattern 4. AbsoluteRelative Wavenumber Intensity Intensity 2952.4532 0.953 0.003 2923.01490.912 0.087 2923.0149 0.912 0.087 2853.1668 0.945 0.024 2177.7444 0.9910.003 2177.7444 0.991 0.003 2134.4653 0.989 0.009 1953.93 0.991 0.0071742.2199 0.992 0.003 1684.2966 0.988 0.008 1601.1227 0.988 0 1523.99030.988 0.004 1494.8295 0.987 0.002 1457.1297 0.974 0.026 1376.8764 0.9830.007 1362.1338 0.985 0.002 1338.7981 0.987 0.001 1315.6263 0.989 0.0011228.4413 0.986 0.002 1191.3421 0.983 0.002 1163.1826 0.982 0.0081081.7777 0.984 0.003 1026.5845 0.982 0.009 965.9176 0.983 0.005 949.6990.985 0.001 848.3372 0.986 0.003 768.2207 0.983 0.008 734.2275 0.9860.001 710.1008 0.985 0.001 686.0188 0.987 0.002 665.3046 0.985 0.003616.5624 0.985 0.001 546.6271 0.98 0.009 526.3169 0.982 0.004 487.2140.979 0.018 472.8975 0.983 0.001 438.7736 0.982 0.006 407.2507 0.9840.003

TABLE 50 FT-IR peak list for AP1189 edisylate Pattern 5. AbsoluteRelative Wavenumber Intensity Intensity 3474.8306 0.986 0.001 3411.04140.984 0 3359.3266 0.981 0.003 3174.2727 0.98 0.016 2472.9486 0.99 0.0032428.6704 0.99 0.004 2346.2568 0.991 0.003 2304.5187 0.99 0.0032256.8486 0.99 0.005 2237.9225 0.994 0 2199.0413 0.987 0.008 2153.650.987 0.009 1979.1896 0.992 0.004 1674.6247 0.964 0.02 1635.7648 0.960.036 1562.1009 0.986 0.002 1524.5681 0.964 0.025 1495.236 0.976 0.011445.9543 0.979 0.011 1427.2528 0.987 0.002 1412.9172 0.987 0.0041353.4254 0.976 0.015 1297.1385 0.987 0.005 1241.464 0.972 0.0151191.238 0.967 0.023 1134.2407 0.975 0.005 1080.2047 0.979 0.0051025.609 0.95 0.043 1025.609 0.95 0.043 1008.4288 0.979 0.002 972.14720.976 0.011 888.5929 0.988 0.005 851.0858 0.984 0.008 775.0492 0.9680.021 734.6082 0.969 0.013 734.6082 0.969 0.013 701.1599 0.979 0.006701.1599 0.979 0.006 680.0768 0.985 0.001 608.8946 0.97 0.007 577.01930.97 0.004 555.0791 0.962 0.022 500.426 0.969 0.004 490.8807 0.969 0.013459.2056 0.973 0.005 459.2056 0.973 0.005 449.358 0.973 0.004 408.82470.976 0.008

TABLE 51 FT-IR peak list for AP1189 nitrate Pattern 1. Absolute RelativeWavenumber Intensity Intensity 3406.5302 0.962 0.013 3366.0481 0.9670.003 3323.5268 0.967 0.001 3212.388 0.961 0.001 3163.9009 0.957 0.0383127.5574 0.962 0.003 3005.5918 0.971 0 2913.8193 0.974 0.005 2871.32170.978 0.001 1680.7274 0.91 0.054 1680.7274 0.91 0.054 1624.0671 0.8990.095 1528.6756 0.915 0.059 1528.6756 0.915 0.059 1497.3045 0.932 0.0341497.3045 0.932 0.034 1466.4331 0.957 0.005 1447.1912 0.939 0.031447.1912 0.939 0.03 1384.114 0.9 0.078 1384.114 0.9 0.078 1359.83470.909 0.015 1331.1636 0.907 0.023 1242.2081 0.953 0.006 1186.1164 0.9220.045 1186.1164 0.922 0.045 1154.2162 0.942 0.009 1132.4738 0.937 0.021081.0367 0.947 0.011 1048.6406 0.959 0.007 1038.6568 0.956 0.0141003.3579 0.963 0.007 975.7122 0.916 0.059 936.6737 0.961 0.009 889.58810.962 0.017 851.0713 0.957 0.023 851.0713 0.957 0.023 820.317 0.9520.025 820.317 0.952 0.025 781.2615 0.943 0.03 781.2615 0.943 0.03753.3192 0.951 0.013 728.8132 0.927 0.02 684.2259 0.922 0.029 641.23750.935 0.005 607.5582 0.915 0.014 574.157 0.923 0.002 554.4784 0.9150.004 523.0893 0.91 0.019 473.9605 0.901 0.045

TABLE 52 FT-IR peak list for AP1189 cyclamate Pattern 2 AbsoluteRelative Wavenumber Intensity Intensity 3327.5952 0.894 0.015 3256.70620.896 0.005 3133.7961 0.861 0.101 3051.8543 0.9 0.003 2926.2906 0.8730.049 2852.1869 0.897 0.02 1681.758 0.816 0.086 1623.3821 0.737 0.2161623.3821 0.737 0.216 1623.3821 0.737 0.216 1623.3821 0.737 0.2161529.9469 0.745 0.192 1494.8375 0.836 0.08 1445.9552 0.819 0.1041415.3786 0.903 0.016 1353.8559 0.845 0.091 1336.4044 0.856 0.0211296.3806 0.894 0.034 1264.8937 0.922 0.005 1242.4293 0.895 0.0171184.9897 0.742 0.018 1156.8898 0.727 0.193 1134.2283 0.744 0.0181083.0619 0.84 0.023 1029.6039 0.583 0.357 1029.6039 0.583 0.357974.7489 0.79 0.1 903.7209 0.922 0.007 889.7243 0.878 0.046 864.53680.866 0.069 850.5855 0.867 0.033 836.2203 0.908 0.013 784.6589 0.8270.065 751.7587 0.818 0.029 700.9984 0.722 0.055 630.931 0.735 0.005605.618 0.677 0.216 559.4107 0.76 0.011 530.7647 0.749 0.052 471.41970.74 0.113 455.4746 0.767 0.028 410.2427 0.837 0.024

TABLE 53 FT-IR peak list for AP1189 cyclamate Pattern 4 AbsoluteRelative Wavenumber Intensity Intensity 3604.5853 0.935 0.007 3343.7280.852 0.036 3257.5858 0.868 0.007 3129.6006 0.825 0.127 3042.9076 0.8710.01 2921.4146 0.831 0.067 2850.5435 0.857 0.036 2133.8407 0.95 0.0032005.1942 0.955 0.012 1714.6479 0.927 0.006 1680.2622 0.728 0.1361623.7709 0.65 0.268 1607.6163 0.658 0.066 1529.9951 0.653 0.2541496.3013 0.77 0.113 1446.2453 0.746 0.151 1358.0905 0.779 0.1221336.0631 0.812 0.053 1295.8377 0.862 0.033 1264.2435 0.872 0.0121243.4692 0.829 0.032 1187.9086 0.642 0.24 1165.1333 0.65 0.04 1132.11030.701 0.023 1080.3651 0.783 0.051 1031.1931 0.507 0.409 1031.1931 0.5070.409 1031.1931 0.507 0.409 972.5047 0.727 0.116 908.6013 0.876 0.017889.2883 0.812 0.068 889.2883 0.812 0.068 869.394 0.809 0.088 851.44270.817 0.045 851.4427 0.817 0.045 837.7939 0.865 0.021 800.6091 0.8220.041 783.2208 0.754 0.103 752.268 0.756 0.054 701.8152 0.639 0.113672.5668 0.657 0.014 640.3004 0.647 0.024 610.5714 0.586 0.268 555.10120.691 0.017 529.8224 0.691 0.043 472.8574 0.66 0.135 413.9675 0.7960.009

TABLE 54 FT-IR peak list for AP1189 cyclamate Pattern 5 AbsoluteRelative Wavenumber Intensity Intensity 3330.1338 0.845 0.025 3257.86030.847 0.007 3128.0082 0.787 0.091 3050.923 0.842 0.005 3015.2804 0.8450.006 2923.7029 0.729 0.224 2852.3392 0.775 0.056 1683.2005 0.746 0.1191621.6978 0.651 0.015 1607.4517 0.642 0.252 1528.9946 0.631 0.2871494.4844 0.763 0.107 1445.2176 0.727 0.157 1415.5026 0.85 0.0281353.5039 0.768 0.132 1336.1138 0.79 0.026 1296.8249 0.839 0.0521265.711 0.882 0.008 1242.2991 0.848 0.022 1183.5642 0.656 0.0261155.3181 0.64 0.02 1131.4271 0.625 0.169 1083.7773 0.716 0.0141029.0064 0.472 0.439 1029.0064 0.472 0.439 971.4767 0.68 0.102 904.60850.874 0.013 889.124 0.8 0.074 865.1575 0.789 0.105 865.1575 0.789 0.105865.1575 0.789 0.105 837.8596 0.851 0.014 784.4749 0.75 0.119 784.47490.75 0.119 752.6207 0.748 0.055 700.5195 0.634 0.033 659.5072 0.6230.027 606.4863 0.549 0.302 555.7751 0.651 0.027 530.6326 0.663 0.043469.1368 0.639 0.154 453.1841 0.681 0.033 408.2296 0.747 0.04

TABLE 55 FT-IR peak list for AP1189 besylate Pattern 1. AbsoluteRelative Wavenumber Intensity Intensity 3381.0336 0.893 0.053 3335.71290.912 0.006 3262.156 0.906 0.017 3166.2704 0.87 0.011 3128.0067 0.8670.111 3053.0452 0.911 0.007 3017.5919 0.916 0.005 2770.6051 0.953 0.0031727.6199 0.956 0.014 1683.2305 0.825 0.09 1661.1658 0.877 0.0171625.152 0.753 0.206 1614.6217 0.758 0.024 1526.8978 0.724 0.2381495.0095 0.848 0.073 1456.8814 0.854 0.043 1443.6263 0.818 0.1251350.1157 0.835 0.116 1334.7203 0.876 0.022 1334.7203 0.876 0.0221299.5393 0.909 0.03 1266.1667 0.933 0.009 1243.167 0.924 0.0111203.5849 0.787 0.014 1187.6114 0.745 0.036 1162.458 0.745 0.0831123.4106 0.658 0.309 1123.4106 0.658 0.309 1098.2649 0.81 0.0211033.8037 0.727 0.183 1015.9959 0.715 0.214 996.3734 0.782 0.115966.4141 0.772 0.137 921.5827 0.933 0.008 891.0203 0.886 0.07 850.94370.898 0.058 784.81 0.828 0.11 751.3821 0.765 0.113 730.5034 0.703 0.172688.9137 0.717 0.031 670.5872 0.697 0.034 648.9273 0.689 0.056 628.63120.702 0.024 608.8258 0.647 0.259 608.8258 0.647 0.259 568.5532 0.6630.127 552.345 0.674 0.023 485.2531 0.788 0.053 469.715 0.724 0.151453.4275 0.809 0.024

TABLE 56 FT-IR peak list for AP1189 oxalate Pattern 1. Absolute RelativeWavenumber Intensity Intensity 3425.6525 0.99 0.007 2950.9765 0.989 02263.6431 0.993 0.007 2224.0341 0.993 0.007 2189.4208 0.992 0.0022094.4029 0.992 0.007 2051.0775 0.992 0.011 2033.9801 0.997 0.0031999.5002 0.994 0.003 1999.5002 0.994 0.003 1985.8891 0.996 0 1678.82940.974 0.013 1629.9945 0.954 0.041 1531.0679 0.96 0.025 1495.3869 0.9670.014 1448.2014 0.976 0.008 1365.3126 0.973 0.014 1334.8102 0.978 0.0061299.4122 0.967 0.022 1271.9425 0.982 0.001 1245.3147 0.982 0.0041193.0299 0.964 0.025 1142.4289 0.98 0.006 1107.9208 0.969 0.0181082.1335 0.972 0.006 1041.1368 0.978 0.009 1002.3102 0.985 0.003972.8647 0.96 0.029 972.8647 0.96 0.029 972.8647 0.96 0.029 936.03220.985 0.003 913.8475 0.988 0.001 891.0902 0.976 0.011 853.3722 0.9740.006 797.5541 0.953 0.002 775.2629 0.941 0.033 775.2629 0.941 0.033775.2629 0.941 0.033 717.0275 0.919 0.041 698.1751 0.937 0.011 662.38450.949 0.004 639.5379 0.936 0.015 610.0509 0.916 0.045 560.327 0.9220.022 478.1393 0.878 0.084 478.1393 0.878 0.084 448.8653 0.935 0.015412.7337 0.95 0.011

TABLE 57 FT-IR peak list for AP1189 oxalate Pattern 2. Absolute RelativeWavenumber Intensity Intensity 3469.2855 0.966 0.015 3388.4016 0.9720.007 3208.2501 0.969 0 3178.2688 0.964 0.005 3081.3694 0.964 0.0251717.1041 0.972 0.002 1676.3502 0.94 0.013 1638.0497 0.892 0.0961638.0497 0.892 0.096 1606.9259 0.92 0.006 1584.1888 0.929 0.0061526.4462 0.9 0.05 1526.4462 0.9 0.05 1496.0078 0.93 0.024 1496.00780.93 0.024 1446.6016 0.945 0.019 1411.6974 0.962 0.005 1350.7637 0.9350.037 1297.892 0.961 0.01 1268.8868 0.972 0.002 1219.9916 0.933 0.0061195.0947 0.922 0.055 1133.3026 0.946 0.01 1109.5923 0.949 0.0021078.7344 0.948 0.01 1040.2025 0.959 0.005 1009.5453 0.967 0.002970.6392 0.937 0.036 889.7046 0.97 0.012 849.9818 0.963 0.019 838.32750.976 0.002 783.9531 0.944 0.025 750.869 0.946 0.019 711.2381 0.8940.084 711.2381 0.894 0.085 632.4438 0.95 0.01 607.1294 0.947 0.006532.9389 0.93 0.011 476.4709 0.913 0.053

TABLE 58 FT-IR peak list for AP1189 oxalate Pattern 4. Absolute RelativeWavenumber Intensity Intensity 3461.2741 0.94 0.007 3433.1516 0.94 0.0053401.1149 0.939 0.003 3401.1149 0.939 0.003 3118.5203 0.916 0.0571714.3801 0.927 0.005 1675.5708 0.87 0.023 1621.3503 0.822 0.0711605.3663 0.825 0.008 1525.658 0.811 0.105 1525.658 0.811 0.105 1494.2040.842 0.039 1444.5779 0.848 0.049 1414.708 0.885 0.01 1351.0291 0.8540.055 1335.9272 0.863 0.007 1297.156 0.872 0.025 1188.4546 0.829 0.0811162.4208 0.854 0.004 1127.9079 0.843 0.022 1080.6836 0.856 0.0141039.6416 0.865 0.015 1001.676 0.883 0.002  970.2682 0.837 0.053 888.3688 0.874 0.028  849.9282 0.864 0.039  783.2574 0.841 0.052 749.7977 0.853 0.024  699.2885 0.788 0.052  631.9542 0.823 0.01 608.1246 0.812 0.017  570.4806 0.815 0.002  543.3487 0.794 0.01 513.8479 0.793 0.009  466.0991 0.747 0.05  444.8321 0.76 0.007

TABLE 59 FT-IR peak list for AP1189 (+)-camphor- 10-sulfonic acidPattern 1 Absolute Relative Wavenumber Intensity Intensity 3340.51460.896 0.022 3269.6418 0.901 0.011 3133.0809 0.857 0.119 3047.6991 0.920.003 3013.6744 0.916 0.006 2958.3394 0.905 0.025 2919.5524 0.919 0.0022889.1522 0.93 0.002 2828.226 0.951 0.001 2774.1878 0.954 0.001 1746.6020.779 0.179 1683.0383 0.754 0.139 1625.0654 0.666 0.278 1529.6827 0.6520.299 1495.1053 0.813 0.095 1455.3026 0.802 0.122 1455.3026 0.802 0.1221445.0707 0.81 0.023 1416.4506 0.891 0.041 1391.8206 0.914 0.0171352.9555 0.781 0.152 1336.8328 0.849 0.025 1296.9587 0.879 0.0431282.3231 0.886 0.011 1226.9819 0.862 0.021 1190.9074 0.666 0.2561167.1669 0.683 0.06 1152.9806 0.69 0.018 1134.1984 0.724 0.0161134.1984 0.724 0.016 1134.1984 0.724 0.016 1134.1984 0.724 0.0161134.1984 0.724 0.016 1134.1984 0.724 0.016 1134.1984 0.724 0.0161040.839 0.529 0.434 1040.839 0.529 0.434 1040.839 0.529 0.434 1006.95160.883 0.021  975.42 0.79 0.135  936.6847 0.937 0.008  889.5805 0.890.068  850.4344 0.873 0.081  786.0655 0.752 0.15  753.8361 0.794 0.058 729.8806 0.758 0.083  701.7408 0.676 0.208  651.2693 0.72 0.012 634.9463 0.709 0.022  608.3725 0.684 0.097

TABLE 60 FT-IR peak list for AP1189 oxoglutarate Pattern 1 AbsoluteRelative Wavenumber Intensity Intensity 3434.1072 0.973 0.008 3316.280.973 0.005 3079.0769 0.965 0.024 2748.1019 0.974 0.001 1974.6528 0.9790.015 1744.1048 0.973 0.004 1725.7973 0.965 0.004 1711.8043 0.955 0.0121682.1477 0.936 0.043 1622.6454 0.937 0.012 1599.5051 0.936 0.0331529.649 0.935 0.056 1529.649 0.935 0.053 1498.9929 0.954 0.0181447.8637 0.963 0.012 1393.3645 0.956 0.017 1393.3645 0.956 0.0171360.1431 0.95 0.026 1336.6705 0.957 0.005 1336.6705 0.957 0.0051298.4765 0.973 0.001 1229.0516 0.968 0.008 1190.0286 0.944 0.0341159.4946 0.953 0.018 1132.3278 0.964 0.007 1080.9647 0.955 0.0211027.079 0.973 0.007 1000.7884 0.978 0.002  969.5172 0.958 0.023 969.5172 0.958 0.023  930.5613 0.977 0.004  890.4947 0.972 0.009 828.1089 0.96 0.017  828.1089 0.96 0.017  813.6562 0.973 0.001 779.5765 0.95 0.031  779.5765 0.95 0.032  754.0045 0.961 0.009 711.9895 0.951 0.022  642.9228 0.964 0.004  624.4739 0.967 0.002 606.95 0.964 0.006  589.2528 0.969 0.001  560.2316 0.97 0.006  532.24740.967 0.01  467.9573 0.967 0.012  412.8724 0.971 0.012

TABLE 61 FT-IR peak list for AP1189 DL mandelic acid Pattern 2 AbsoluteRelative Wavenumber Intensity Intensity 3324.9282 0.82 0.119 3152.89170.841 0.014 3069.0933 0.823 0.057 3040.9086 0.824 0.002 3015.6015 0.8250.001 2979.4458 0.827 0.003 2933.1051 0.84 0.015 2874.4871 0.865 0.0092786.4381 0.871 0.001 2748.2612 0.871 0.001 2646.4095 0.878 0.0012609.8399 0.878 0.003 2588.4994 0.879 0.003 1699.5562 0.748 0.0371674.6619 0.463 0.397 1674.6619 0.463 0.397 1643.6605 0.579 0.061606.2055 0.687 0.059 1579.8052 0.734 0.056 1524.8976 0.448 0.4851524.8976 0.448 0.485 1494.5467 0.631 0.18 1494.5467 0.631 0.181454.4981 0.687 0.141 1404.3973 0.733 0.093 1360.7749 0.542 0.0691346.1451 0.493 0.354 1346.1451 0.493 0.354 1294.554 0.771 0.0441270.4268 0.83 0.014 1270.4268 0.83 0.014 1246.9404 0.824 0.0431193.6969 0.575 0.305 1135.9058 0.771 0.055 1114.6922 0.741 0.0911080.9246 0.714 0.146 1042.4307 0.661 0.211 1002.6618 0.825 0.045 974.7184 0.599 0.284  974.7184 0.599 0.284  929.9534 0.733 0.157 889.4518 0.74 0.135  850.1391 0.662 0.219  783.2 0.518 0.346  755.52910.618 0.208  734.8637 0.524 0.292  704.2896 0.44 0.398  646.4857 0.510.047  635.2889 0.51 0.206  561.6984 0.661 0.041

TABLE 62 FT-IR peak list for AP1189 DL-mandelic acid Pattern 3 AbsoluteRelative Wavenumber Intensity Intensity 3438.9914 0.945 0.004 3414.25460.945 0.002 3305.8784 0.934 0.001 3029.7727 0.921 0.05 2736.8009 0.9360.001 1676.8694 0.871 0.044 1676.8694 0.871 0.044 1624.7713 0.862 0.0681605.7456 0.87 0.006 1579.8096 0.885 0.007 1525.2321 0.839 0.1221525.2321 0.839 0.122 1493.2721 0.87 0.036 1453.0437 0.887 0.0281406.6532 0.895 0.016 1348.6562 0.854 0.065 1335.9744 0.858 0.0021294.6387 0.896 0.01 1237.9816 0.91 0.005 1191.3174 0.868 0.0531191.3174 0.868 0.053 1191.3174 0.868 0.053 1132.5099 0.895 0.0091132.5099 0.895 0.009 1114.6238 0.896 0.004 1080.2331 0.888 0.021056.0946 0.896 0.006 1028.7992 0.897 0.003 1001.0851 0.913 0.005 971.5213 0.879 0.04  930.8348 0.902 0.022  888.9418 0.905 0.02 888.9418 0.905 0.02  849.8642 0.89 0.036  781.182 0.866 0.047  750.39940.877 0.016  733.4775 0.864 0.013  699.6274 0.834 0.063  699.6274 0.8340.063  634.7914 0.853 0.009  606.2778 0.849 0.018  568.7299 0.858 0.002 532.1813 0.858 0.003  510.4669 0.856 0.008  469.0286 0.836 0.038 469.0286 0.836 0.038  451.8363 0.844 0.009  407.8772 0.862 0.01

TABLE 63 FT-IR peak list for AP1189 hippuric acid Pattern 1 AbsoluteRelative Wavenumber Intensity Intensity 3478.5092 0.986 0.004 3462.85850.987 0.002 3391.5891 0.98 0.014 3351.9339 0.983 0.003 2019.2428 0.9880.01 1692.0022 0.965 0.016 1625.0168 0.953 0.026 1625.0168 0.953 0.0261573.5216 0.97 0.005 1560.279 0.972 0.001 1523.7117 0.952 0.0421483.5359 0.963 0.015 1453.7204 0.974 0.004 1445.2105 0.973 0.0111395.626 0.953 0.034 1395.626 0.953 0.034 1348.9271 0.971 0.0121320.0629 0.98 0.003 1296.3458 0.98 0.002 1272.1234 0.985 0.0021243.1359 0.983 0.003 1199.7151 0.973 0.015 1165.661 0.983 0.0031136.9015 0.98 0.008 1114.0689 0.984 0.002 1082.649 0.982 0.0061042.5752 0.987 0.004  982.3329 0.98 0.011  938.7359 0.985 0.005 888.4103 0.982 0.007  850.5125 0.981 0.009  783.0247 0.979 0.011 751.2867 0.975 0.007  729.0162 0.977 0.005  708.0583 0.967 0.003 696.2757 0.966 0.024  656.1822 0.973 0.009  637.5248 0.975 0.004 599.4983 0.976 0.005  576.4886 0.975 0.003  552.808 0.973 0.009 552.808 0.973 0.009  517.638 0.978 0.003  489.6767 0.973 0.005 467.5258 0.967 0.021  434.7231 0.975 0.007

TABLE 64 FT-IR peak list for AP1189 formic acid Pattern 1 AbsoluteRelative Wavenumber Intensity Intensity 3432.3814 0.874 0.059 2981.66440.826 0.129 2812.6797 0.836 0.033 2723.0736 0.852 0.015 2631.8709 0.8570.013 1676.7328 0.763 0.047 1627.8235 0.584 0.226 1605.8813 0.663 0.0181581.7727 0.741 0.007 1531.3788 0.582 0.318 1531.3788 0.582 0.3181493.4246 0.626 0.148 1493.4246 0.626 0.148 1447.5484 0.711 0.0781351.0058 0.58 0.348 1351.0058 0.58 0.348 1296.5694 0.798 0.03 1271.93680.835 0.018 1242.541 0.824 0.042 1199.1381 0.669 0.205 1138.5633 0.7990.019 1120.1193 0.727 0.114 1081.2687 0.762 0.077 1043.2571 0.789 0.064 999.926 0.847 0.024  973.6776 0.682 0.209  935.6882 0.864 0.019 890.7174 0.801 0.094  851.1643 0.801 0.021  807.8253 0.725 0.059 767.7829 0.633 0.201  712.4497 0.582 0.284  712.4497 0.582 0.238 698.69 0.6 0.029  640.9999 0.697 0.057  610.1032 0.674 0.105  610.10320.674 0.105  594.6837 0.736 0.009  545.17 0.683 0.078  486.8537 0.7310.033  472.0881 0.681 0.103  448.1613 0.733 0.05  403.3132 0.771 0.003

TABLE 65 FT-IR peak list for AP1189 L-lactic acid Pattern 1 AbsoluteRelative Wavenumber Intensity Intensity 3443.026 0.899 0.022 3301.66030.841 0.122 3104.1943 0.855 0.006 3077.6911 0.848 0.037 2980.2002 0.870.015 2964.0623 0.876 0.005 2930.9886 0.889 0.006 2865.3491 0.891 0.0012846.9568 0.888 0.013 2790.497 0.892 0.002 2748.4106 0.891 0.0012685.0933 0.894 0.004 1703.147 0.711 0.162 1678.0314 0.715 0.1011625.7241 0.631 0.188 1607.9149 0.703 0.037 1527.4719 0.564 0.3881527.4719 0.564 0.388 1495.0557 0.684 0.108 1458.6145 0.693 0.1431445.9522 0.703 0.069 1403.0228 0.741 0.091 1359.487 0.668 0.1841359.487 0.668 0.184 1336.7196 0.752 0.051 1291.4634 0.749 0.1151270.3898 0.832 0.01 1237.741 0.848 0.025 1200.7797 0.734 0.1431165.9727 0.845 0.022 1119.7668 0.659 0.225 1089.3157 0.769 0.0421043.8629 0.783 0.106 1031.9237 0.838 0.013  975.0628 0.711 0.189 956.7339 0.794 0.066  956.7339 0.794 0.066  888.356 0.826 0.077 876.9653 0.874 0.008  848.4237 0.721 0.15  796.0445 0.819 0.013 775.3283 0.708 0.161  750.9077 0.712 0.14  717.6257 0.618 0.193 700.7775 0.675 0.041  656.2251 0.745 0.024  633.1683 0.701 0.045 611.8089 0.658 0.118  586.2594 0.669 0.05  532.3279 0.701 0.019

TABLE 66 FT-IR peak list for AP1189 DL-lactic acid Pattern 1 AbsoluteRelative Wavenumber Intensity Intensity 3282.8423 0.848 0.114 3137.22940.891 0.002 3106.7371 0.878 0.007 3078.3359 0.874 0.026 3054.1371 0.8760.003 2980.1703 0.887 0.016 2959.8998 0.886 0.019 2928.186 0.906 0.0062863.9284 0.907 0.01 2830.9054 0.914 0.001 2767.7562 0.911 0.0021706.6962 0.769 0.13 1677.4684 0.777 0.089 1628.5031 0.704 0.1671606.954 0.769 0.032 1527.8575 0.642 0.325 1527.8575 0.642 0.3251494.7078 0.744 0.096 1494.7078 0.744 0.096 1456.7346 0.751 0.1241446.5759 0.758 0.027 1409.4495 0.755 0.114 1409.4495 0.755 0.1141359.0736 0.728 0.16 1336.0661 0.8 0.04 1299.0075 0.825 0.075 1284.08120.848 0.01 1269.9398 0.876 0.009 1237.0916 0.883 0.024 1202.4033 0.780.132 1168.1212 0.879 0.02 1118.8217 0.697 0.219 1088.5536 0.819 0.0481046.0438 0.799 0.12 1046.0438 0.799 0.12 1046.0438 0.799 0.12 1032.04920.873 0.012 1000.5308 0.911 0.007  975.3702 0.747 0.182  975.3702 0.7470.182  957.32 0.837 0.064  887.9494 0.86 0.071  877.4801 0.897 0.011 848.442 0.755 0.17  827.5387 0.842 0.018  797.1482 0.851 0.026 775.3905 0.776 0.109  750.5948 0.757 0.132  718.7205 0.669 0.174 718.7205 0.669 0.174

TABLE 67 FT-IR peak list for AP1189 glutaric acid Pattern 1 AbsoluteRelative Wavenumber Intensity Intensity 3451.4823 0.909 0.051 3273.85990.904 0.035 3247.2814 0.908 0.001 3213.4294 0.908 0.005 2950.2826 0.8840.09 2772.9078 0.908 0.002 1983.7185 0.959 0.001 1945.1815 0.956 0.011912.7557 0.958 0.004 1681.2131 0.733 0.119 1632.9309 0.694 0.2031608.0157 0.79 0.018 1555.0838 0.833 0.029 1525.973 0.679 0.273 1525.9730.679 0.273 1493.208 0.753 0.082 1493.208 0.753 0.082 1453.6917 0.7650.12 1453.6917 0.765 0.12 1411.5581 0.797 0.084 1411.5581 0.797 0.0841347.2594 0.773 0.016 1340.1909 0.771 0.137 1306.3792 0.834 0.0381265.4491 0.856 0.047 1223.6023 0.766 0.045 1192.895 0.728 0.1371148.2185 0.704 0.212 1148.2185 0.704 0.212 1081.9008 0.812 0.0431041.9241 0.824 0.044 1024.5139 0.83 0.019  997.3686 0.859 0.017 969.7962 0.784 0.105  926.2335 0.868 0.048  889.0404 0.889 0.037 889.0404 0.889 0.037  852.9313 0.827 0.092  804.882 0.811 0.037 785.2951 0.749 0.136  785.2951 0.749 0.136  785.2951 0.749 0.136 751.9143 0.744 0.132  751.9143 0.744 0.132  727.2603 0.746 0.125 682.267 0.746 0.07  640.5213 0.77 0.055  640.5213 0.77 0.055  610.34210.801 0.039  520.4538 0.75 0.051

TABLE 68 FT-IR peak list for AP1189 glutaric acid Pattern 2 AbsoluteRelative Wavenumber Intensity Intensity 3430.3134 0.879 0.076 3288.17820.887 0.052 3209.4296 0.905 0.008 3132.4855 0.911 0.008 3113.8608 0.9110.004 3016.0295 0.878 0.093 2941.5484 0.884 0.025 2922.1175 0.889 0.0122872.472 0.906 0.005 2769.5575 0.902 0.014 1678.217 0.671 0.1461630.5087 0.636 0.248 1552.6043 0.798 0.045 1527.0178 0.612 0.3251493.0553 0.67 0.138 1452.4984 0.712 0.136 1409.1509 0.762 0.0931352.9723 0.691 0.205 1352.9723 0.691 0.205 1318.4605 0.804 0.0281318.4605 0.804 0.028 1298.4179 0.83 0.029 1267.3811 0.835 0.0491229.3818 0.752 0.043 1194.241 0.642 0.213 1131.5232 0.615 0.2841131.5232 0.615 0.284 1131.5232 0.615 0.284 1081.7286 0.706 0.0581047.651 0.772 0.024 1047.651 0.772 0.024 1047.651 0.772 0.024 1026.37250.78 0.04 1011.9658 0.808 0.013  967.7876 0.745 0.114  926.12 0.8020.096  889.4235 0.836 0.066  852.4417 0.747 0.149  802.3239 0.762 0.059 802.3239 0.762 0.059  782.8912 0.642 0.227  782.8912 0.642 0.227 752.8624 0.706 0.134  724.9698 0.638 0.213  702.3892 0.718 0.076 665.9727 0.695 0.02  641.3229 0.66 0.148  609.8383 0.756 0.033 550.6147 0.558 0.342  550.6147 0.558 0.342

What is claimed is:
 1. A crystalline Form of anN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalt selected from the group consisting of: i. a crystalline Form A ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumacetate exhibiting at least X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation at 11.5±0.2,23.5±0.2, and 27.0±0.2, ii. a crystalline Form B ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsuccinate exhibiting at least X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation at 9.7±0.2,22.8±0.2, and 26.7±0.2, iii. a crystalline Form C ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumtosylate exhibiting at least X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation at 14.5±0.2,21.0±0.2, and 25.2±0.2, iv. a crystalline Form D ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumfumarate exhibiting at least X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation at 17.6±0.2,21.2±0.2, and 26.3±0.2, v. a crystalline Form I ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumacetate exhibiting X-ray lines (2-theta values) in a powder diffractionpattern when measured using Cu K_(α) radiation at 23.5±0.2, 24.2±0.2,and 26.9±0.2, vi. a crystalline Form II ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumexhibiting X-ray lines (2-theta values) in a powder diffraction patternwhen measured using Cu K_(α) radiation at 13.3±0.2, 21.1±0.2, and23.1±0.2, vii. a crystalline Form III ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumnapadisylate exhibiting at least X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiation at13.4±0.2, 22.2±0.2, and 26.8±0.2, viii. a crystalline Form IV ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumnapadisylate exhibiting at least X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiation at5.4±0.2, 15.6±0.2, and 23.4±0.2, ix. a crystalline Form V ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumesylate exhibiting at least X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation at 14.5±0.2,16.5±0.2, and 18.6±0.2, x. a crystalline Form VI ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumedisylate exhibiting at least X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation at 4.8±0.2,12.8±0.2, and 16.5±0.2, xi. a crystalline Form VII ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumedisylate exhibiting at least X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation at 6.1±0.2,15.7±0.2, and 23.6±0.2, xii. a crystalline Form VIII ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumedisylate exhibiting at least X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation at 15.5±0.2,20.7±0.2, and 21.7±0.2, xiii. a crystalline Form IX ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumedisylate exhibiting at least X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation at 4.5±0.2,16.7±0.2, and 24.7±0.2, xiv. a crystalline Form X ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumnitrate exhibiting at least X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation at 15.3±0.2,21.4±0.2, and 25.1±0.2, xv. a crystalline Form XI ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumcyclamate exhibiting at least X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation at 7.0±0.2,13.8±0.2, and 15.7±0.2, xvi. a crystalline Form XII ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumcyclamate exhibiting at least X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation at 7.3±0.2,15.3±0.2, and 17.9±0.2, xvii. a crystalline Form XIII ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumcyclamate exhibiting at least X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation at 15.3±0.2,18.5±0.2, and 18.7±0.2, xviii. a crystalline Form XIV ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumbesylate exhibiting at least X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation at 13.0±0.2,15.1±0.2, and 19.9±0.2, xix. a crystalline Form XV ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumoxalate exhibiting at least X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation at 19.5±0.2,23.3±0.2, and 25.8±0.2, xx. a crystalline Form XVI ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumoxalate exhibiting at least X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation at 17.1±0.2,17.9±0.2, and 19.6±0.2, xxi. a crystalline Form XVII ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumoxalate exhibiting at least X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation at 6.3±0.2,10.6±0.2, and 19.8±0.2, xxii. a crystalline Form XVIII ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine(+)-camphor-10-sulfonic acid exhibiting at least X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation at 6.5±0.2, 11.5±0.2, and 14.8±0.2, xxiii. a crystalline FormXIX ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumoxoglutarate exhibiting at least X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiation at16.8±0.2, 23.4±0.2, and 23.6±0.2, xxiv. a crystalline Form XX ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidineDL-mandelic acid exhibiting at least X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiation at14.8±0.2, 24.2±0.2, and 25.5±0.2, xxv. a crystalline Form XXI ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidineDL-mandelic acid exhibiting at least X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiation at5.4±0.2, 10.0±0.2, and 24.6±0.2, xxvi. a crystalline Form XXII ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinehippuric acid exhibiting at least X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiation at20.1±0.2, 24.1±0.2, and 24.5±0.2, xxvii. a crystalline Form XXIII ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumformate exhibiting at least X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation at 13.3±0.2,15.1±0.2, and 25.6±0.2, xxviii. a crystalline Form XXIV ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidineL-lactic acid exhibiting at least X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiation at3.8±0.2, 9.9±0.2, and 11.9±0.2, xxix. a crystalline Form XXV ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidineDL-lactic acid exhibiting at least X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiation at9.8±0.2, 11.9±0.2, and 27.6±0.2, xxx. a crystalline Form XXVI ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidineglutaric acid exhibiting at least X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiation at8.3±0.2, 15.9±0.2, and 21.9±0.2, xxxi. a crystalline Form XXVII ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidineglutaric acid further exhibiting one or more X-ray lines (2-thetavalues) in a powder diffraction pattern when measured using Cu K_(α)radiation selected from the group consisting of 16.9±0.2, 25.6±0.2,27.1±0.2, 28.2±0.2, and 28.7±0.2, xxxii. a crystalline Form XXVIII ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidineglutaric acid exhibiting at least X-ray lines (2-theta values) in apowder diffraction pattern when measured using Cu K_(α) radiation at14.2±0.2, 16.9±0.2, and 24.5±0.2, and xxxiii. a crystalline Form XXIX ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidineadipic acid exhibiting at least X-ray lines (2-theta values) in a powderdiffraction pattern when measured using Cu K_(α) radiation at 13.4±0.2,14.5±0.2, and 25.5±0.2.
 2. The crystalline Form of theN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalt according to claim 1, wherein the crystalline Form is selected fromthe group consisting of: i. the crystalline Form A ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumacetate, ii. the crystalline Form B ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsuccinate, iii. the crystalline Form XIV ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumbesylate, iv. the crystalline Form XIX ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumoxoglutarate, v. the crystalline Form XX ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidineDL-mandelic acid, vi. the crystalline Form XXII ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidinehippuric acid, vii. the crystalline Form XXIII ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumformate, viii. the crystalline Form XXIV ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidineL-lactic acid, ix. the crystalline Form XXV ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidineDL-lactic acid, x. the crystalline Form XXVI ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidineglutaric acid, and xi. the crystalline Form XXIX ofN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidineadipic acid.
 3. A method of treating a disease or disorder in a subjectin need thereof, said method comprising administering the crystallineForm of theN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalt according to claim 1 to the subject.
 4. The method according toclaim 3, wherein the disease or disorder is an arthritic disease, akidney disease, a cardiovascular disease, atherosclerosis, a viraldisease or disorder, or a systemic inflammatory disorder.
 5. The methodaccording to claim 4, wherein the arthritic disease is selected from thegroup consisting of: i. an auto-immune disease and/or an inflammatorydisease that presents with joint inflammation, ii. inflammatoryarthritis, iii. degenerative arthritis, iv. metabolic arthritis, v.reactive arthritis, vi. infectious arthritis, and vii. arthritis as partof a systemic inflammatory disease.
 6. The method according to claim 5,wherein the inflammatory arthritis is Rheumatoid Arthritis, optionallywherein said subject is a subject with an inappropriate response tomethotrexate (MTX).
 7. The method according to claim 4, wherein thekidney disease is selected from the group consisting of: i. kidneydisease presenting with proteinuria, ii. proteinuric kidney disease,iii. glomerular disease, iv. nephrotic syndrome (glomerulonephrosis), v.primary nephrotic syndrome (primary glomerulonephrosis), vi. secondarynephrotic syndrome (secondary glomerulonephrosis), vii. an inflammatorykidney disease, viii. glomerulonephritis (GN), and ix. idiopathicmembranous nephropathy (iMN).
 8. The method according to claim 4,wherein the viral disease or disorder is selected from the groupconsisting of: i. a symptomatic viral disease or disorder, ii. asymptomatic viral disease or disorder with inflammation, iii. aninflammatory viral disease or disorder, iv. a viral respiratoryinfection, v. a viral respiratory disease or disorder, vi. a viraldisease or disorder of the lung, vii. a viral disease or disorder withinflammation in the respiratory system, viii. a viral disease ordisorder with one or more respiratory symptoms, ix. severe disease, x.critical disease, xi. viral pneumonia, xii. viral bronchiolitis, xiii.viral diseases or disorders with respiratory failure, xiv. acuterespiratory distress syndrome (ARDS), xv. viral acute respiratorydistress syndrome (ARDS), xvi. symptomatic COVID-19 with acuterespiratory distress syndrome (ARDS), xvii. a viral disease or disorderwith systemic inflammatory distress syndrome (SIDS) and/or sepsis,xviii. a viral disease or disorder with pulmonary insufficiency, xix. aviral disease or disorder with cytokine release syndrome (CRS) and/or acytokine storm (hypercytokinemia), and xx. a viral disease or disordercaused by a viral infection selected from the group consisting of SevereAcute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2); SARS-CoV,MERS-CoV, the dengue virus and influenza virus (including Type A, Type Band Type C).
 9. A method for producing the crystalline Form of theN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalt according to claim 1, comprising: i. mixing i.N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine andan acid or salt thereof in a solvent to form a mixture, ii. anN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalt and an acid or salt thereof in a solvent to form a mixture, iii. anamorphous form or a second crystalline form of theN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalt in a solvent to form a composition, iv.3-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl]-propanal, amino guanidine or asalt thereof, and an acid or a salt thereof in a solvent to form amixture, or v.N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine or asecondN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalt and a counter ion of an acid on an ion exchange column; and ii.isolating the crystalline Form of theN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalt from said mixture, composition, or ion exchange column.
 10. Themethod according to claim 9, said method comprising: i. mixingN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine andan acid or salt thereof in a solvent to form a mixture; and ii.isolating the crystalline Form of theN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalt from said mixture.
 11. The method according to claim 9, said methodcomprising: i. mixing a secondN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalt and an acid or a salt thereof in a solvent to form a mixture; andii. isolating the crystalline Form of theN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalt from the mixture.
 12. The method according to claim 9, said methodcomprising: i. mixing an amorphous form or a second crystalline form ofthe N-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalt in a solvent to form a composition; and ii. isolating thecrystalline Form of theN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalt from said composition.
 13. The method according to claim 9, saidmethod comprising: i. mixing3-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl]-propanal, amino guanidine or asalt thereof, and an acid or a salt thereof in a solvent, and ii.isolating the crystalline form of theN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalt from said composition.
 14. The method according to claim 9, saidmethod comprising: i. providingN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine or asecondN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalt, ii. introducing a counter ion of an acid ion using ion exchange,and iii. isolating the crystalline Form of theN-{3-[1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidiniumsalt.
 15. The method according to claim 9, wherein the acid or the saltthereof is selected from the group consisting of: acetic acid, succinicacid, fumaric acid, toluene sulfonic acid, naphthalene-1,5-disulfonicacid, ethanesulfonic acid, ethane-1,2-disulfonic acid, nitric acid,cyclohexylsulfamic acid, benzenesulfonic acid, oxalic acid,(+)-camphor-10-sulfonic acid, 2-oxoglutaric acid, hydroxy(phenyl)aceticacid such as DL-hydroxy(phenyl)acetic acid, N-benzoylglycine, formicacid, 2-hydroxypropanoic acid such as L-2-hydroxypropanoic acid orDL-2-hydroxypropanoic acid, pentanedioic acid, and hexanedioic acid, andsalts thereof.
 16. The method according to claim 9, wherein the solventis a protic or a polar aprotic solvent.
 17. The method according toclaim 9, wherein the mixture or the composition is heated at least oncebefore the isolating step.
 18. The method according to claim 9, whereinthe mixture or the composition is heated and cooled in cycles for 15 minto 72 hours before the isolating step.
 19. The method according to claim9, further comprising a step of adding an anti-solvent to the mixture orthe composition before the isolation step.
 20. The method according toclaim 9, wherein the isolation is carried out using filtration,centrifugation, and/or evaporation of the solvent or solvents.